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 Table of Contents  
REVIEW ARTICLE
Year : 2010  |  Volume : 2  |  Issue : 8  |  Page : 341-352

Mathematical modeling the neuroregulation of blood pressure using a cognitive top-down approach


Montague Healthcare, Mulberry House, 6 Vine Farm Close, Cotgrave, Nottingham NG12 3TU, United Kingdom

Date of Web Publication9-Nov-2011

Correspondence Address:
Graham Wilfred Ewing
Director, Montague Healthcare, Mulberry House, 6 Vine Farm Close, Cotgrave, Nottingham NG12 3TU
United Kingdom
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Source of Support: None, Conflict of Interest: None


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  Abstract 

Background: The body's physiological stability is maintained by the influence of the autonomic nervous system upon the dynamic interaction of multiple systems. These physiological systems, their nature and structure, and the factors which influence their function have been poorly defined. A greater understanding of such physiological systems leads to an understanding of the synchronised function of organs in each neural network i.e. there is a fundamental relationship involving sensory input and/or sense perception, neural function and neural networks, and cellular and molecular biology. Such an approach compares with the bottom-up systems biology approach in which there may be an almost infinite degree of biochemical complexity to be taken into account. Aims: The purpose of this article is to discuss a novel cognitive, top-down, mathematical model of the physiological systems, in particular its application to the neuroregulation of blood pressure. Results: This article highlights the influence of sensori-visual input upon the function of the autonomic nervous system and the coherent function of the various organ networks i.e. the relationship which exists between visual perception and pathology. Conclusions: The application of Grakov's model may lead to a greater understanding of the fundamental role played by light e.g. regulating acidity, levels of Magnesium, activation of enzymes, and the various factors which contribute to the regulation of blood pressure. It indicates that the body's regulation of blood pressure does not reside in any one neural or visceral component but instead is a measure of the brain's best efforts to maintain its physiological stability.

Keywords: Mathematical modeling, physiological systems, blood pressure, autonomic nervous system.


How to cite this article:
Ewing GW. Mathematical modeling the neuroregulation of blood pressure using a cognitive top-down approach. North Am J Med Sci 2010;2:341-52

How to cite this URL:
Ewing GW. Mathematical modeling the neuroregulation of blood pressure using a cognitive top-down approach. North Am J Med Sci [serial online] 2010 [cited 2020 Oct 26];2:341-52. Available from: https://www.najms.org/text.asp?2010/2/8/341/86671


  Introduction Top


The body's physiological stability is maintained by the dynamic interaction of multiple systems. These physiological systems regulate specific functions e.g. O2/CO2 levels in the blood; temperature; the absorption of minerals, vitamins and nutrients by the digestive tract; blood glucose; blood pressure; blood volume; elimination of wastes; etc. They influence the rates of reaction and extraction processes in the body. The ability of light to activate proteins is influenced by, and/or influences, these systems. Altered levels of minerals or ions e.g. of Magnesium or Sodium, permeate the cell membrane and alter the electrochemical characteristics of the cells and neurons i.e. their voltage gradients, and the firing ability of neurons.

Mono-chromatic light influences many of the body's physiological processes. The precise selection of light and/or colour selects those neurons which are sensitised and part of neurophysiological processes [1] . It influences the function of neurons in the brain and biological processes in the visceral organs e.g.

  • it regulates the function of retinal photoreceptors [2],[3] and the flow of chloride through biological membranes [4] . This use of light has been able to halt brain activity in specific neurons using different colours [5],[6] and influence the timing of neural networks i.e. the firing of neurons. In halorhodopsin different colours stimulate different processes e.g. green light initiates chloride transport and blue light induces proton pumping [1] . In addition, light influences synapse development [7] .
  • it activates gene expression [8] and mitochondrial DNA replication [9] .
  • it regulates the autonomic nervous system [10],[11] and the stability of the physiological systems.
  • it regulates bilirubin metabolism [12],[13] , the production of calcitriol [14],[15] , and their various isomers. The action of light upon the skin produces calcitriol (1α,25 dihydroxyvitamin D3 ) which is involved in brain function, synthesis of neurotransmitters, brain detoxification pathways, and has a significant neuroprotective and immunomodulatory effect [16],[17] .
  • it activates enzymes, which catalyse the body's function [18],[19] , and influences the (i) production of Nitric Oxide [20] and subsequent regulation of blood pressure and lipid peroxidation; (ii) migration of stem cells [21] ; (iii) rate of wound healing [22],[23] ; (iv) rate at which proteins translocate to the cell membrane [18] ; (v) function of the lymphatic system [24] ; (vi) regulation of intercellular pH balance [25],[26] ; (vii) blood flow [27] and heart rate [28] ; (viii) sperm motility [29] ; (ix) sexual function [30] ; (x) immune function [31],[32],[33] , etc.


The principle appears increasingly evident. Monochromatic light, received from the environment (and/or generated and transmitted in vivo), raises proteins to their activated state [19] . It may be essential for their subsequent reaction. The light emitted from such reactions explains the often observed, although hitherto unexplained, link between pathology and colour perception. The delivery of monochromatic light stimulates specific biochemical processes and regulates the function of the physiological systems [34],[35] . It synchronises the activity of groups of neurons [36] and their electrical impulses [37] . Whilst each physiological system has a primary function, by contrast most organs are multi-functional and are components in different physiological systems therefore instability in one system invariably influences the stability of other systems. Accordingly, measurements of visual perception reflect the actual rate of reactions between proteins and their substrates rather than their total level i.e. the rate of biophoton emission can be a measure of pathology.


  Regulation of Blood Pressure Top


The prevailing understanding of blood pressure is within that of a cardiovascular system however there may be a need to revise this definition as (i) blood pressure, (ii) blood volume, (iii) breathing, and (iv) plasma glucose and other systems. Any mathematical model of blood pressure must take into account the various factors which directly and indirectly influence its function. Considering the issues from the perspective of a physiologically controlled system and fluid mechanics this suggests the need to include (i) neural regulation of blood pressure; (ii) feedback from baroreceptors located in the blood vessels; (iii) quality (and its viscosity), volume and pressure of blood; (iv) condition of blood vessels, their ability to handle the pressure, to ensure the smooth (parallel or turbulent) flow of blood, and to ensure a satisfactory supply of blood (and oxygen) to the brain (including partial occlusions) and visceral organs e.g. the heart; (v) influence of the autonomic nervous system (including sensory stimulii), the endocrine glands (pituitary, thyroid and adrenal) and the visceral organs which are part of the blood pressure system i.e. the heart, spleen and liver; (vi) nervous system feedback from the visceral organs and of neural components within this biofeedback system e.g. the cerebellum; and (vii) the extent of atherosclerosis.

The stability of each system involves the coordinated function of a considerable number of hormones [38] or substrates. In the case of blood pressure this involves e.g. catecholamines, aldosterone, oxytocin and vasopressin, acetylcholine, renin, angiotensin II, natriuretic peptides, vasopressin, nitric oxide, serotonin, GABA, ouabain, neuropeptide Y, opioids, bradykinin, thyrotropin-releasing factor, vasoactive intestinal polypeptide, tachykinins, histamine, corticotropin-releasing factor, melatonin, and fatty-acids.

Existing models largely exclude (i) the cumulative influence of memories, the impact of stress upon blood pressure, and the influence of the autonomic nervous system upon the function of neural structures; (ii) the role of the cerebellum; (iii) the influence of the body's biochemistry upon the firing of neurons and/or the reactivity of proteins with their substrates; (iv) and overlooks the inherent assumptions, limitations and errors in biochemical testing i.e. sampling time, variability between equipment, sampling errors, environmental context, genetic variations [39] , patient age, etc.

To understand whether this revised understanding of physiological systems and mathematical model of blood pressure [11] withstands rescrutiny the objective herein is to consider each aspect of such a sophisticated mechanism.

Brain

The evidence suggests that stress-induced alterations to the hypothalamic pathways influence the regulation of short and long-term levels of sympathetic activity i.e. alterations in the levels of neurotransmitters and hormones increase sympathetic nervous activity and lead to a rise in blood pressure. The magnitude or longevity of this influence leads to altered homeostasis and changes to the homeostatic memory. This suggests that hypothalamic changes in hypertension are a link in an integrated response to sensory input, predominating as the kidney's impaired ability to excrete sodium and ultimately as high blood pressure. In particular, the medulla oblongata [40],[41] and dorsomedial hypothalamus influence the control of cardiovascular, respiratory and other physiological responses to acute stress [42] . Other neural structures or brain regions involved in regulating blood pressure include the amygdala [43],[44] , periaqueductal grey matter [45] , cerebellum [46],[47] , pituitary, etc. In addition, electrical stimulation of brain centres can produce arrhythmias [48] , ventricular fibrillation [49] , etc. The level around which arterial pressure fluctuates or is regulated i.e. the 'neural set point', varies according to context. It is, therefore, maintained at a level which seeks to best maintain the body's physiological stability and its function.

Such observations may be adapted e.g. (i) cryogenic blockade of the forebrain, posterior hypothalamus, or Fields of Forel inhibits ventricular fibrillation [49] ; (ii) electrical stimulation of the brain [45] ; (iii) pulsed light therapies [34] activate the neural centres and influence high blood pressure; and (iv) meditation reduces blood pressure [50] .

The Neuroregulation of blood pressure - The maintenance of 'normal' blood pressure regulates the supply of oxygen to the neural tissues and visceral organs [51] . It is essential to the body's stability and function: deviations being associated with cognitive impairment, migraine, dementia, stroke, diabetes mellitus, cardiovascular disorders, depression, sleep apnoea, etc. Within the medulla oblongata [40],[41] networks of neurons respond to signals received from baroreceptors and the autonomic nervous system [52],[53] , and regulate blood pressure [54],[55] . They do so by changing heart rate or by contracting (or expanding) specific blood vessels in order to adjust the flow of blood. This is a rapidly adjusting dynamic system: blood pressure rising and falling almost instantaneously according to the body's needs.

What is measured as blood pressure by sphygmomanometer of systolic and diastolic measurements of blood pressure is the bio-physical manifestation of the prevailing biochemistry, and nervous and physiological structures. Blood pressure measurements, although invaluable in medical practice as an indicator of heart function, are the manifestation of the body's pathophysiology however an over-reliance upon blood pressure measurements may restrict consideration of the wide variety of contexts e.g. genetic [56],[57],[58] , environmental [59],[60],[61] , and gender [62],[63] . In addition, the level of cholesterol is influenced by the neuroregulation of the autonomic nervous system [64] . Altered neuroregulation may lead to different levels of ldl and hdl cholesterol thereby influencing blood viscosity and blood pressure.

The regulation of blood pressure by the autonomic nervous system is heavily influenced by stress [65] - Stress influences all aspects of cognition [66] . In particular, there is a link between cognition and pathology [67] . Stress is any combination of influences which exceeds the body's natural tolerance limits [68],[69],[70] . It influences the central nervous system [71],[72] ; subsequently induces biochemical dysfunction; and influences the regulation of organ function, and cellular and molecular biology [73] . It suppresses the immune [74] and endocrine [75] response(s). This generates reactive-oxygen species, which is manifest as oxidative stress [76] and subsequently as a ladder of pathologies [77] which progressively influence systemic stability. Accordingly any mathematical model of the physiological systems should consider all factors which influence the autonomic nervous system e.g. light and/or sensori-visual input.

Brain function includes brain physiology; regulation of the key physiological system and between physiological systems; sensory input, the storage (and retrieval) of memories, cognitive and behavioural consequences [78]

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Sensory input, conveyed primarily by visual means, influences the hypothalamic-pituitary axis and other neural structures. The information received by the brain is processed and distributed via the neural networks to the visceral organs. Signal(s) returned to the brain indicate the body's physiological preparedness for activity and are processed and ultimately manifest as behaviour.

Regulation of blood pressure, and cardiovascular dysfunction, is influenced by stress and is now widely researched. Different stresses influence e.g.

  • the measurement of blood pressure [79] ,
  • the brain's ability to function [80] and regulate biophysical processes [81] ,
  • the risk of hypertension has been linked to psychosocial factors [82] ,
  • the occurrence of acute coronary events has been linked to emotional trauma [83] ,
  • the occurrence of coronary heart disease has been linked to loneliness and/or social isolation [84],[85] ,
  • the progression of carotid atherosclerosis has been linked to feelings of hopelessness [86] ,
  • an increased risk of cardiovascular disease has been linked to distrust [87] ,
  • the occurrence of coronary heart disease has been linked to anger [88],[89] ,
  • dysfunction of the left ventricle has been linked to grief, bereavement and a broken-heart [90] ,
  • the occurrence of coronary heart disease has been linked to stress in the workplace [91],[92] ,
  • the risk of myocardial infarction in men has been linked to lack of exposure to sunlight [93] ,
  • the lack of calcitriol in non-insulin dependent diabetes has been linked to the prevalence of cardiovascular disease [94] .


In brief, stress is mainly due to the consequences of lifestyle e.g. poor diet/increased weight, lack of exposure to sunlight [93],[94] , domestic and/or work-related stressors, etc. By contrast, and in support of the above, 'alternative' measures to reduce stress have been shown to reduce morbidity and mortality e.g. (i) the body requires a balanced supply of all key antioxidants. Vitamin deficiencies can be damaging to the body's function. An excess of vitamins can be as damaging as a deficiency. Vitamins C, D (calcitriol) & E influence blood pressure [95],[96],[97] . (ii) L ight therapies [34] , including exposure to natural sunlight, stimulate calcitriol production and regulate the body's function. (iii) Alternative approaches e.g. exercise [98] , dietary interventions [99],[100] , meditation [101],[102] and hypnosis, and stress management interventions [103] reduce morbidity and mortality [104],[105] and encourage normal physiological development [106] . (iv) Surgical approaches e.g. deep brain stimulation [45],[107],[108] , have been developed which stimulate brain tissues.

Cognitive impairment is associated with the development of diabetes [109] , the subsequent development of high blood pressure [110],[111],[115] , heart dysfunction [112],[113],[114] , increased age [115] , and increased weight [116] . A decreased ability to deliver oxygen to the brain is a significant factor in the development of migraine, dementia [117],[118] and neurodegenerative conditions. Specific cognitive impairment e.g. to colour perception [109],[110] , memory [116] , hearing deficits [119],[120] , olfactory deficits [121] , etc; have been linked to cardiovascular deterioration or disease. There is a clear link between cognition and that of molecular and cellular biology [11],[122],[123] .

Organs involved in the regulation of blood pressure: brain, pituitary, thyroid and adrenal glands, liver, heart, spleen, and blood and peripheral blood vessels

Visceral Organs

a. Apart from the pituitary gland which is the sole endocrine gland in the sleep system, the three primary endocrine glands are active in all other physiological systems. This indicates the value of sleep.

  • Insufficient sleep i.e. too little (or too much) sleep or poor quality sleep, will suppress the function of the pituitary gland and influence the function of all other physiological systems.
  • Light influences the function of the pituitary gland [124] and influences the function of the thyroid and adrenals i.e. the hypothalamic-pituitary axis.
  • Reduced levels of calcitriol are suspected of lowering levels of parathyroid hormone and may increase blood pressure [97] .
  • Adrenaline produces rhythmic contractions of the spleen [125] and reduces the blood volume retained by the spleen.
  • angiotensinogen levels in the liver are increased by thyroid hormone, corticosteroids, oestrogen and the enzyme angiotensin II.
  • Overproduction of renin and its manifestation as high blood pressure has been linked to the production of cortisol [126] .


Organs involved in the regulation of sleeping pattern: brain, pituitary gland, spinal cord, peripheral nervous system, ear and nose.

b. The quality of blood and the condition of blood vessels influence the body's function. Blood viscosity is the manifestation of its various components e.g. plasma glucose, fatty acids, cholesterol, etc.

  • The greater blood viscosity the greater will be the energy required for the heart to pump blood through the lungs and to the brain.
  • The slower will be the diffusion of oxygen through the blood and its subsequent absorption by haemoglobin i.e. the harder it will be to absorb oxygen.
  • Increased blood viscosity will impair/slow ventricular filling [127] .
  • Increased levels of fatty acids, cholesterol, plasma glucose, etc; will increase blood viscosity and will slow the circulation of blood and its subsequent processing in organs e.g. pancreas, kidneys, liver, etc. This will inevitably slow metabolic rate, the generation of energy, etc. Some components have increased risk of precipitation and accumulation in the blood vessels and a greater 'stickiness' i.e. ability to adhere to blood vessel walls [128] .
  • Increased blood viscosity will slow the dissociation of proteins and substrates to and from their receptor sites thereby reducing rate of reaction and what we recognise as metabolic rate.
  • Chronic and/or mild acidosis is the consequence of stress, lack of exercise and/or of obesity. It influences the ability to absorb minerals in the digestive tract.
  • The condition of the blood vessels influences the ability of the heart to pump blood to the brain, failures of which can lead to haemorrhagic stroke [129] .
  • High levels of cholesterol and fatty acids may lead to atherosclosis [130],[131] .


c. The heart pumps blood through the lungs and delivers oxygen to the brain. An adequate supply of oxygen is essential for the condition and function of all muscles and tissues in the body and, in particular, the musculature of the heart, liver and kidneys. The heart pumps the complete contents of the blood system around the body typically every c20 seconds. The pumping of blood through the brain, lungs and to the skin are essential for the body's ability to regulate: temperature, the ratio of CO2/O2, pH, and absorption of nutrients and minerals by the intestines; and the conditions which influence the rate of all enzymatic processes in the body.

d. The liver produces the hormone, angiotensinogen, which raises blood pressure in response to low blood pressure. The levels of angiotensinogen are influenced by the function of the endocrines. Blockages in the liver e.g. due to cirrhosis, (perhaps due to the congestion arising from fatty acid deposition) are likely to lead to portal hypertension.

e. The influence of the spleen upon the regulation of blood pressure is widely acknowledged although there is not an accepted understanding of its role [132],[133],[134] . There is a relationship between hypertension, retention of blood in the spleen [135] and the autonomic nervous system [136],[137] . The spleen's main function is to maintains a reservoir of blood and ensure the availability of blood in extreme circumstances [138] , known as splenic extravasation, which influences blood pressure [139] .

The inter-relationship between Physiological Systems

That there is a sophisticated inter-relationship between physiological systems is implicit. Each of the systems are characterised by its higher or lower function. They are dynamically inter-related i.e. higher function in one system is linked to higher (or lower) function in another system e.g. between blood pressure and breathing or between blood pressure and blood volume, however that they are independent systems is supported by noting that instability in one system is not necessarily supported by instability in other systems. The network of systems (see [Table 1]) can reconfigure or compensate for instability in one system, OR can reconfigure at an anomalous level as the chronic condition (i.e. a pathological functional system). This may be responsible for baffling results e.g. the results from histopathological tests may be indicative of a medical condition yet the patient may not exhibit any symptoms, and vice-versa.

The regulation of blood pressure is influenced by, or influences, other physiological systems e.g. sleep [140],[141],[142] , sexual function [143] , breathing [144] , elimination of fluids, pH, plasma glucose [145],[146],[147] , etc. If overweight people with chronic kidney disease and/or cardiovascular disease have too little exercise this will influence (i) plasma CO2/O2 levels and pH; (ii) reduce adrenal function and inhibit the elimination of fluids (thereby influencing sodium levels and osmotic pressure in the cells); (iii) increase insulin resistance [148] ; and (iv) destabilise sleeping patterns [149] . This is often the consequence of poor diet [128],[150],[151] . Moreover, low levels of exposure to natural sunlight will suppress the normal function of the pituitary gland and the generation of calcitriol in the skin.
Table 1: Related physiological systems

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Different medications act upon specific pathophysiologies e.g. beta-blockers moderate the function of the adrenals; calcium channel blockers reduce blood volume; diuretics act upon the kidney to reduce blood volume and levels of sodium; ACE inhibitors act upon the kidney and block the action of angiotensin-converting enzyme.

There is not a 100% association between chronic kidney disease and cardiovascular disease [152],[153] . High blood pressure occurs in an estimated 80% of patients with chronic kidney disease [154] although hypertension can occur without its occurrence, sometimes in quite extraordinary circumstances [155] . This suggests that regulation of blood pressure is subject to the influence of multiple variables, some of which have a greater or lesser influence according to their significance to each physiological system i.e. kidney dysfunction may be both the cause and the consequence of high blood pressure [156],[157] . This can only arise as a consequence of a dynamic, multi-systemic association.

Biochemical insufficiencies throughout the body will inevitably influence different aspects of the body's function e.g. factors influencing the gastrointestinal absorption [158] and/or retention of minerals [155],[159],[160] , and perhaps also vitamins and/or hormones, and fatty acids. In particular, Magnesium deficits have been linked to a wide range of conditions including mitral valve prolapse [161],[162] , coronary heart disease [163] , hypertension [164] , cardiac arrythmias, [165] , congestive heart failure [166] , diabetes mellitus [167],[168] , migraines and epilepsy [169] , fibromyalgia [170] , asthma [171] , attention deficit disorder [172],[173] , pre-eclampsia [174] , etc.

Lowered digestive pH reduces the levels of intestinal flora which are required to sustain the absorption of minerals at a satisfactory level. A Magnesium deficit is associated with the stress-mechanisms e.g. increasing the level of adrenaline and related corticosteroids, raising blood pressure [175] . Mg is required to activate muscle contractions e.g. in the heart, intestines, etc. Without an adequate supply of Mg the muscles and organs cannot function properly and remain in a contracted state. Lowered pH influences the nature and bioavailability of minerals: acid salts e.g. of phosphoric acid, bind with minerals (magnesium and calcium) in the digestive tract to form salts that are not absorbed [176] . The consumption of acidified soft drinks (pH typically 2.5) have been linked to the occurrence of chronic kidney disease [177] , beer has a pH of typically 3.5.

The regulation of renin i.e. angiotensinogenase by the kidney and angiotensinogen in the liver is fundamental to the regulation of blood pressure. The reaction of these components produces angiotensin which causes constriction of blood vessels and raises blood pressure. There is a close association between the function of the endocrine glands and the renin-angiotensin system e.g. (i) angiotensinogen levels are increased by thyroid hormone, corticosteroid, oestrogen and angiotensin II levels; (ii) angiotensin stimulates the production of aldosterone from the adrenal cortex; and (iii) the pituitary hormone vasopressin influences the re-absorption of water into the blood (and hence the volume of urine). This influences the levels of minerals, in particular sodium and potassium, the osmotic pressure of the cells and intercellular communication. Accordingly any factors which influence the function of the endocrines will inevitably influence blood pressure. In particular, light activates enzymes; stimulates the production of pituitary hormones by the pituitary gland and calcitriol by the skin; the production of Nitric Oxide [20] and the subsequent regulation of blood pressure and lipid peroxidation. Light is therefore an essential component in the body's regulation.


  Discussion Top


This cognitive top-down model takes into account the cognitive influence of sensory input, memory and behaviour. It is based upon the concept that the body is a wholly biochemical organism and hence that all aspects of cognition must reflect the underlying biochemistry and bio-physical processes. It includes the influence of weight, age and sex upon the body's function: each pathology being expressed as a multi-component vector within a biomathematical matrix.

All mathematical models are estimates of varying precision therefore each cannot be expected to be entirely accurate. In this case we can dispute the accuracy of the predicted influence of weight and age. Furthermore it appears to be quite extraordinary that a cognitive technique could provide such huge amounts of data [178] . Every technique will have its benefits and weaknesses. Nevertheless the cognitive approach developed appears to offer a unique perspective regarding the diagnosis of disease, perhaps able to identify the nature and progression of disease more accurately than has hitherto been possible using conventional histopathological test methods.

This model considers that the brain acts as a neural matrix processing multi-sensory input from its external and internal environments, the consequence being its sensory output i.e. behaviour, and that the body acts as a visceral matrix: the organs being structured in arrays of synchronised and interdependent systems in which instability, the consequence of stress(es), is expressed as pathologies. Such methodology has been incorporated into a commercialised technology. As described, virtual scanning arises from a top-down cognitive mathematical model whereas most systems biology is based upon bottom-up biochemical models: the essential difference being that the cognitive model considers the top-down approach to be pre-eminent i.e. that systemic dysfunction is expressed as a biochemical dysfunction or pathology(s). Further evidence of this dynamic relationship is evident by noting how the cerebellum influences blood pressure yet paradoxically the body's function is able to continue when this neural component is removed. Moreover the cerebellum processes as much information as the rest of the brain. This can only be so if the cerebellum is involved in processing the feedback of data from the viscera to the brain i.e. the Purkinje cells of the cerebellum facilitate the feedback of data from all organs to the neural centres [179] . Accordingly, the loss of this function would enable the brain to continue to function although with progressive loss of regulation and onset of pathologies.

The cognitive approach recognises the influence of sensory input upon the neural matrix and subsequently upon the stability of the physiological systems and the autonomic nervous system. It has been a challenge for medical research to accept that stress, in its many and various forms, could alter the autonomic nervous system sufficiently to be responsible for raising blood pressure and the development of heart disease. It is reasonable to understand how the concept of a cardiovascular physiological system could have arisen. There is clearly a close association and interdependence of the physiological systems incorporating the coordinated function of the organs. In the case of blood pressure there is a close association with the regulation of blood volume and breathing but, as discussed, there is also the influence and inter-dependence of most other physiological systems. It may be too simplistic to consider that regulation of blood pressure is solely regulated by specific neural systems or components/organs [180] or of specific biochemistries e.g. the renin-angiotensin system, but instead that there is a complex system comprising neural regulation and biofeedback [81],[181] in which the renin-angiotensin system is most prevalent.

It is reasonable to conclude that there is a central regulating function but paradoxically it is also reasonable to conclude that such a mechanism does not reside in any one neural component or matrix of components but instead is a reflection of the brain's overall ability to maintain its function and/or stability [49] - and the function and stability of the various organ networks. The degree of function e.g. renal denervation [182],[183] or severe baroreceptor dysfunction 184 , alters blood pressure and/or enables other regulatory systems to take over. Inhibition of other neural centres by the significant influence of sensory input, which is often discounted in orthodox systems biology, alters the degree of regulation.


  Acknowledgements Top


The author thanks the many researchers who, through their work, have contributed to this article.

 
  References Top

1.Gerber U. Metabotropic glutamate receptors in vertebrate retina. Doc Ophthalmol 2003;106:83-87.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Binder BM, Biernbaum MS, Bownds MD. Light activation of one rhodopsin molecule causes the phosphorylation of hundreds of others. A reaction observed in electropermeabilized frog rod outer segments exposed to dim illumination. J Biol Chem 1990; 265:15333-15340.   Back to cited text no. 2
[PUBMED]  [FULLTEXT]  
3.Kolbe M, Besir H, Essen L-O, Oesterhelt D. Structure of the light-driven chloride pump halorhodopsin at 1.8 A resolution. Science 2000;288:1390-1396.  Back to cited text no. 3
    
4.Chow BY, Han X, Dobry AS, Qian X, Chuong AS, Li M, Henninger MA, Belfort GM, Lin Y, Monahan PE, Boyden ES. High-Performance Genetically-Targetable Optical Neural Silencing by Light-Driven Proton Pumps. Nature 2010;463(7277):98-102.  Back to cited text no. 4
    
5.Polland HJ, Franz MA, Zinth W, Kaiser W, Hegemann P, Oesterhelt D. Picosecond events in the photochemical cycle of the light-driven chloride-pump halorhodopsin. Biophys. J 1985;47(1):55-59.  Back to cited text no. 5
    
6.Igarashi H, Inomata K. Effects of Low-Power Gallium Aluminium Arsenide Diode Laser Irradiation on the Development of Synapses in the Neonatal Rat Hippocampus. Acta Anatomica 1991;140:150-155.  Back to cited text no. 6
[PUBMED]    
7.Bamberg E, Tittor J, Oesterhelt D. Light-driven proton or chloride pumping by halorhodopsin. Proc. Natl. Acad. Sci. U S A 1993;90:639-43.  Back to cited text no. 7
    
8.Cruz FG, Koh JT, Link KH. Light-Activated Gene Expression. J Am Chem Soc 2000;122(36):8777-8778.   Back to cited text no. 8
    
9.Vacca RA, Marra E, Quagliariello E, Greco M. Activation of Mitochondrial DNA Replication by He-Ne Laser Irradiation. Biochem Biophys Res Commun 1993;195(2):704-709.  Back to cited text no. 9
    
10.Krakov SV. Colour Vision and the Autonomic Nervous System. J Opt Soc Am 1941;31(4):335-337.  Back to cited text no. 10
    
11.Ewing GW, Ewing EN. Cognition, the Autonomic Nervous System and the Physiological Systems. J Biogenic Amines 2008;22(3):85-162.  Back to cited text no. 11
    
12.Cremer RJ, Perryman PW, Richards DH . Influence of Light on the Hyperbilirubinemia in Infants. Lancet 1958;1:1094-1097.  Back to cited text no. 12
[PUBMED]    
13.Sisson T. Visible Light Therapy of Neonatal Hyperbilirubinemia. Photochemical and Photobiological Reviews 1976;1:241-268.  Back to cited text no. 13
    
14.Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr 2004;79(3):362-371.  Back to cited text no. 14
    
15.Holick MF. Vitamin D Deficiency. N Engl J Med 2007;357:266-281.  Back to cited text no. 15
[PUBMED]  [FULLTEXT]  
16.Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab 2002;13(3):100-105.  Back to cited text no. 16
    
17.Hayes DP. The protection afforded by vitamin D against low radiation damage. International Journal of Low Radiation 2008;5(4):368-394(27).  Back to cited text no. 17
    
18.Levskaya A, Weiner OD, Lim WA, Voigt CA. Spatiotemporal control of cell signaling using a light-switchable protein interaction. Nature 2009;461:997-1001.   Back to cited text no. 18
[PUBMED]  [FULLTEXT]  
19.Shimomura O, Chalfie M, Tsien R. The Nobel Prize in Chemistry 2008.  Back to cited text no. 19
    
20.Nagase S, Hirayama A, Ueda A, Oteki T, Takada K, Inoue M, Shimozawa Y, Terao J, Koyama A. Light-Shielded Hemodialysis Prevents Hypotension and Lipid Peroxidation by Inhibiting Nitric Oxide Production. Clin Chem 2005;51:2397-2398.  Back to cited text no. 20
[PUBMED]  [FULLTEXT]  
21.Gasparyan L, Brill G, Makela A. Influence of laser radiation on migration of stem cells. Progress in biomedical optics and imaging 2006;7:(26).  Back to cited text no. 21
    
22.Mester E, Jaszsagi-Nagy E. The Effect of Laser Radiation on Wound Healing and Collagen Synthesis. Studia Biophysica 1973;35(3):227-230.  Back to cited text no. 22
    
23.Horwitz LR, Burke TJ, Carnegie DH. Augmentation of Wound Healing Using Monochromatic Infrared Energy. Adv Skin Wound Care 1999;12:35-40.  Back to cited text no. 23
    
24.Lievens PC. The effect of I.R. Laser irradiation on the vasomotricity of the lymphatic system. Lasers Med Sci 1991;6(2):189-191.  Back to cited text no. 24
    
25.Alexandratou E, Yova D, Handris P, Kletsas D, Loukas S. Human Fibroblasts Altercations induced by low power laser irradiation at the single cell level using confocal microscopy. Photochem Photobiol Sci 2002;1:547-552.  Back to cited text no. 25
[PUBMED]    
26.Opas M, Dziak E. Confocal Microscopy Methods and Protocols 1998;122:305-313.ISBN: 978-0-89603-526-3. Kami T, Yoshimura Y, Nakajima T, Ohshiro T, Fujino T. Effects of Low-Power Diode Lasers on Flap Survival. Ann Plast Surg 1985;14(3):278-283.  Back to cited text no. 26
    
27.Schafer A, Kratky KW. The Effect of Colored Illumination on Heart Rate Variability. Forsch Komplementmed 2006;13:167-173.  Back to cited text no. 27
    
28.Sato H, Landthaler M, Haina D, Schill WB. The Effects of Laser Light on Sperm Motility and Velocity in Vitro. Andrologia 1984;16(1):23-25.  Back to cited text no. 28
    
29.Dewan E, Menkin MF, Rock J. Effects of Photic Stimulation on the Human Menstrual Cycle. Photochem Photobiol 1978;27:581-585.  Back to cited text no. 29
    
30.Young S, Bolton P, Dyson M, Harvey W, Diamantopoulos C. Macrophage Responsiveness to Light Therapy. Lasers Surg Med 1989;9:497-505.  Back to cited text no. 30
[PUBMED]    
31.Roberts, J. Visible Light Induced Changes in the Immune Response through an Eye-Brain Mechanism. Journal of Photochemistry and Photobiology 1995;29:3-15.  Back to cited text no. 31
    
32.Yamaguchi N, Tsukamoto Y. The Effects of Semiconductor Laser Irradiation on the Immune Activities of Human Lymphocytes in Vitro. Lasers in the Life Sciences 1994;6(2):143-149.  Back to cited text no. 32
    
33.Ewing GW. A Theoretical Framework for Photosensitivity: Evidence of Systemic Regulation. Journal of Computer Science and System Biology 2009;2(6):287-297.   Back to cited text no. 33
    
34.Ewing GW. There is a need for an Alternative or Modified Medical Paradigm involving an understanding the nature and significance of the Physiological Systems. North Am J Med Sci 2010;2(6):1-6.  Back to cited text no. 34
    
35.Cox RH, Shealy CN, Cady RK, Liss S. The Journal of Neurological and Orthopaedic Medicine and Surgery 1996;17:32-34.   Back to cited text no. 35
    
36.Bower B. Perception may dance to the beat of collective neuronal rhythms. Science News 1998;153(8):120.  Back to cited text no. 36
    
37.De Wardener HE. The Hypothalamus and Hypertension. Physiol Rev 2001; 81(4):1599-1658.  Back to cited text no. 37
    
38.Weir MR. Races Respond Differently To High Blood Pressure Treatment. American Society of Hypertension scientific meeting in San Francisco May 27-31, 1997.  Back to cited text no. 38
    
39. Colombari E, Sato MA, Cravo SL, Bergamaschi CT, Campos RR, Lopes OU. Role of the Medulla Oblongata in Hypertension. Hypertension 2001; 38:549-554.   Back to cited text no. 39
[PUBMED]  [FULLTEXT]  
40.Howe PR. Blood pressure control by neurotransmitters in the medulla oblongata and spinal cord. J Auton Nerv Syst 1985;12(2-3):95-115.  Back to cited text no. 40
    
41.De Matteo R, Head GA, Mayorov DN. Tempol in the Dorsomedial Hypothalamus Attenuates the Hypertensive Response to Stress in Rabbits. Am J Hypertens 2006;19: 396-402.   Back to cited text no. 41
[PUBMED]  [FULLTEXT]  
42.Galosy RA, Clarke LK, Vasko MR, Crawford IL. Neurophysiology and neuropharmacology of cardiovascular regulation and stress. Neuroscience and Bio-behavioral Reviews 1981;5:l37-75.  Back to cited text no. 42
    
43.Carpeggiani C, Landisman C, Montaron MF, Skinner JE.Cryoblockade in limbic brain (amygdala) prevents or delays ventricular fibrillation after coronary artery occlusion in psychologically stressed pigs. Circ Res 1992;70(3):600-606.  Back to cited text no. 43
    
44.Green AL, Wang S, Owen SL, Xie K, Liu X, Paterson DJ, Stein JF, Bain PG, Aziz TZ. Deep brain stimulation can regulate arterial blood pressure in awake humans. Neuroreport 2005;16(16):1741-1745.  Back to cited text no. 44
    
45.Zanutto BS, Valentinuzzi ME, Segura ET. Neural set point for the control of arterial pressure: role of the nucleus tractus solitarius. Biomed Eng Online 2010, 9:4doi:10.1186/1475-925X-9-4.  Back to cited text no. 45
    
46.Achari NK, Downman CBB. Autonomic effector responses to stimulation of nucleus fastigius. J Physiol 1970;210:637-650.  Back to cited text no. 46
    
47.Skinner JE. Neurocardiology: How Stress Produces Fatal Cardiac Arrhythmias: Arrhythmia: A clinical Approach. Edited by P.J. Podrid and P.R. Kowey; pub. Williams & Wilkins, Baltimore, 1993.   Back to cited text no. 47
    
48.Skinner JE, Reed JC. Blockade of a frontocortical-brainstem pathway prevents ventricular fibrillation of the ischemic heart in pigs. Am J Physiol 1981;240:H156-163.  Back to cited text no. 48
    
49.Paul-Labrador M, Polk D, Dwyer JH, Velasquez I, Nidich S, Rainforth M, Schneider R, Merz CNB. Effects of a randomized controlled trial of transcendental meditation on components of the metabolic syndrome in subjects with coronary heart disease. Arch Intern Med 2006;166:1218-24.  Back to cited text no. 49
    
50.Prakash ES. The Ultimate Goal in Neural Regulation of Cardiovascular Function Revisited. Advan Physiol Edu 2008;32:107-108.   Back to cited text no. 50
    
51.Mark AL. The sympathetic nervous system in hypertension: a potential long-term regulator of arterial pressure. J Hypertension 1996;14:S159-S165.  Back to cited text no. 51
    
52.Mancia G, Grassi G, Parati G, Zanchetti A. The sympathetic nervous system in human hypertension. Acta Physiol Scand Suppl 1997;640:117-121.  Back to cited text no. 52
[PUBMED]    
53.Cravo SL, Campos RR, Colombari E, Sato MA, Bergamaschi CM, Pedrino GR, Ferreira-Neto ML, Lopes OU. Role of the Medulla Oblongata in normal and high arterial blood pressure regulation. An Acad Bras Cienc 2009;81(3):589-603.  Back to cited text no. 53
    
54.Guertenstein PG, Silver A. Fall in Blood Pressure produced from discrete regions of the ventral surface of the medulla by glycine and lesions. J Physiol 1974;242:489-503.  Back to cited text no. 54
    
55.Robbins MA, Elias, MF, Elias PK, Budge MM. Blood Pressure and Cognitive Function in an African-American and a Caucasian-American Sample: The Maine-Syracuse Study. Psychosom Med 2005;67:707-714.   Back to cited text no. 55
    
56.Feskens EJM, Kromhout D. Epidemiological Studies on Eskimos and Fish Intake. Annals of the New York Academy of Sciences 2006; 683: 9-15. (Issue Dietary Lipids and Insulin Action: Proceedings of the Second International Smolenice Insulin Symposium.  Back to cited text no. 56
    
57.Wigertz K, Palacios C, Jackman LA, Martin BR, McCabe LD, McCabe GP, Peacock M, Pratt HJ, Weaver CM. Racial differences in calcium retention in response to dietary salt in adolescent girls. Am J Clin Nutr 2005;81(4):845-850.  Back to cited text no. 57
    
58.Ponchia A, Noventa D, Bertaglia M, Carretta R, Zaccaria M, Miraglia G. Pascotto P, Buja G. Cardiovascular neural regulation during and after prolonged high altitude exposure. Eur Heart J 1994;15(11):1463-1469.   Back to cited text no. 58
    
59.Rowe WJ. The Apollo 15 Space Syndrome. Circulation 1998;97:119-120.  Back to cited text no. 59
[PUBMED]  [FULLTEXT]  
60.Rowe WJ. Obesity or space flight - the heart can't see the difference. Spaceflight 2005; 47:274.  Back to cited text no. 60
    
61.Kauser K, Rubany GM. Vasculoprotection by estrogen contributes to gender differences in cardiovascular diseases: potential mechanism and role of endothelium. In: Rubany GM, Dzau VJ, eds. The Endothelium in Clinical Practice. New York, NY: Marcel Dekker; 1997:439-467.  Back to cited text no. 61
    
62.Harm DL, Jennings RT, Meek JV, Powell MR, Putcha L, Sams CP, Schneider SM, Shackelford LC, Smith SM, Whitson PA. Genome and hormones: gender differences in physiology, Invited review; gender issues related to spaceflight: a NASA perspective. J Appl Physiol 2001;91:2374-2383.  Back to cited text no. 62
    
63.Perez-Tilve D, Hofmann SM, Basford J, Nogueiras R, Pfluger PT, Patterson JT, Grant E, Wilson-Perez HE, Granholm NA, Arnold M, Trevaskis JL, Butler AA, Davidson WS, Woods SC, Benoit SC, Sleeman MW, DiMarchi RD, Hui DY, Tschöp MH. Melanocortin signaling in the CNS directly regulates circulating cholesterol free. Nature Neuroscience Published online 6 June 2010. DOI:10.1038/nn.25  Back to cited text no. 63
    
64.Schwartz, Gerin W, Davidson KW, Pichering TG, Brosschot JF, Thayer JF, Christenfeld N, Linden W. Toward a Causal Model of Cardiovascular Responses to Stress and the Development of Cardiovascular Disease. Psychosom Med 2003;65:22-35.  Back to cited text no. 64
    
65.Waldstein SR, Katzel LI. Stress-induced blood pressure reactivity and cognitive function. Neurology 2005;64:1746-1749.  Back to cited text no. 65
[PUBMED]  [FULLTEXT]  
66.Hock BJ, Lattal KM, Kulnane LS, Abel T, and Lamb BT. Pathology associated memory deficits in Swedish mutant genome-based amyloid precursor protein transgenic mice. Curr Aging Sci 2009;2(3):205-213.  Back to cited text no. 66
    
67.Guyton AC, Hall JE. (2006) Medical Physiology, Elsevier Saunders. 11th edition, pp.211.  Back to cited text no. 67
    
68.Marks AR. Physiological systems under pressure. J Clin Invest 2008;118(2):411-412.  Back to cited text no. 68
    
69.Lattal KM, Bernardi RE. Cellular learning theory: theoretical comment on Cole and McNally. Behav Neurosci 2007;121(5):1140-1143.  Back to cited text no. 69
    
70.Sudakov KV. The basic principles of the general theory of functional systems.íèçìà / Ðóêîâîäñòâî. Medicine 1987;- Ñ. 26-49. S.26-49.  Back to cited text no. 70
    
71.Kryzhanovskii GN, Adrianov OS, Bekhtereva NP, Negovskii VA, Sudakov KV, Khananashvili MM. Integrative activity of the nervous system in health and in disease. Vestnik Rossiĭskoĭ akademii meditsinskikh nauk 02/1995.  Back to cited text no. 71
    
72.Scharf MT, Woo NH, Lattal KM, Young JZ, Nguyen PV, Abel T. Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training. J Neurophysiol 2002;87(6):2770-2777.  Back to cited text no. 72
    
73.Benschop RJ, Geenen R, Mills PJ, Naliboff BD, Kiecolt-Glaser JK, Herbert TB, van der Pompe G, Miller GE, Matthews KA, Godaert GL, Gilmore SL, Glaser R, Heijnen CJ, Dopp JM, Bijlsma JW, Solomon GF, Cacioppo JT. Cardiovascular and immune responses to acute psychological stress in young and old women: a meta-analysis. Psychosom Med 1998;60(3):290-296.  Back to cited text no. 73
    
74.Malarkey WB, Kiecolt-Glaser JK, Pearl D, Glaser R. Hostile behaviour during marital stress alters pituitary and adrenal hormones. Psychosom Med 1994;56(1):41-51.  Back to cited text no. 74
    
75.Pollock DM, Pollock JS. Endothelin and oxidative stress in the vascular system. Curr Vasc Pharmacol 2005;3:365-367.  Back to cited text no. 75
    
76.Player MS, King DE, Mainous AG, Geesey ME. Psychosocial Factors and Progression From Prehypertension to Hypertension or Coronary Heart Disease. Ann Fam Med 2007;5:403-411.  Back to cited text no. 76
    
77.Stoerig P, Cowey A. Visual perception and phenomenal consciousness. Proceedings of the 25th Annual Meeting of the European Brain and Behaviour Society. Behav Brain Res 1995;71(1-2):147-156.  Back to cited text no. 77
    
78.Pickering T, James G, Boddie C, Harshfield G, Blank S, Laragh J. How common is white coat hypertension?. J Am Med Assoc 1988;259 (2):225-228.  Back to cited text no. 78
    
79.Sapolsky RM. Why stress is bad for your brain. Science 1996; 273(5276):749-750.   Back to cited text no. 79
    
80.Skinner JE, Wolf SG, Kresh Y, Izrailtyan I, Armour JA, Huang M-H. Application of chaos theory to a model biological system: Evidence of self-organization in the intrinsic cardiac nervous system. Integr Psychol Behav Sci 1996; 31(2):122-146.  Back to cited text no. 80
    
81.Yan LL, Liu K, Mattews KA, Deviglus ML, Ferguson TF, Kiefe CI. Psychosocial factors and risk of hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study. JAMA 2003;290:2138-2148.  Back to cited text no. 81
    
82.Bhattacharyya MR, Steptoe A. Emotional triggers of acute coronary syndromes: strength of evidence, biological processes, and clinical implications. Prog Cardiovasc Dis 2007;49:353-365.  Back to cited text no. 82
    
83.Brummett BH, Barefoot JC, Siegler IC, Clapp-Channing NE, Lytle BL, Bosworth HB, Williams RB, Mark DB. Characteristics of Socially Isolated Patients with Coronary Artery Disease Who are at Elevated Risk for Mortality. Psychosom Med 2001; 63:267-272.  Back to cited text no. 83
    
84.Kaplan GA, Salonen JT, Cohen RD. Social connections and mortality from all causes and from cardiovascular disease: prospective evidence from Eastern Finland. Am J Epidemiol 1988;128:370-380.  Back to cited text no. 84
    
85.Everson SA, Kaplan GA, Goldberg DE, Salonen R, Salonen JT. Hopelessness and 4-Year Progression of Carotid Atherosclerosis: The Kuopio Ischaemic Heart Disease Risk Factor Study. Arterioscler Thromb Vasc Biol 1997;17:1490-1495.   Back to cited text no. 85
    
86.Ranjit N, Diez-Roux AV, Shea S, Cushman M, Seeman T, Jackson SA, Ni H. Psychosocial factors and inflammation in the Multi-Ethnic Study of Atherosclerosis. Arch Intern Med 2007;167:174-181.  Back to cited text no. 86
    
87.Williams JE Paton CC, Siegler IC, Eigenbrodt ML, Nieto FJ, Tyroler HA. Anger proneness predicts coronary heart disease risk: prospective analysis from the atherosclerosis risk in communities (ARIC) study. Circulation 2000;101:2034-2039.   Back to cited text no. 87
    
88.Chang PP, Ford DE, Meoni LA, Wang N-Y, Klag MJ. Anger in young men and subsequent premature cardiovascular disease: the precursors study. Arch Intern Med 2002;162(8):901-906.   Back to cited text no. 88
    
89.Wittstein IS, Thiemann DR, Lima JAC, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral Features of Myocardial Stunning Due to Sudden Emotional Stress. N Engl J Med 2005;352:539-548.  Back to cited text no. 89
    
90.Aboa-Eboulé C, Brisson C, Maunsell E, Masse B, Bourbonnais R, Vezina M, Milot A, Theroux P, Dagenais GR. Job strain and risk of acute recurrent coronary heart disease events. JAMA 2007; 298(14):1652-1660.  Back to cited text no. 90
    
91.Chandola T, Britton A, Brunner E, Hemingway H, Malik M, Kumari M, Badrick E, Kivimaki M, Marmot M. Work stress and coronary heart disease: what are the mechanisms? Eur Heart J 2008;29(5):640-648.   Back to cited text no. 91
    
92.Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-Hydroxyvitamin D and Risk of Myocardial Infarction in Men A Prospective Study. Arch Intern Med 2008;168(11):1174-1180.  Back to cited text no. 92
    
93.Cigolini M, Iagulli MP, Miconi V, Galiotto M, Lombardi S, Targher G. Serum 25-Hydroxyvitamin D3 Concentrations and Prevalence of Cardiovascular Disease Among Type 2 Diabetic Patients. Diabetes Care 2006;29(3):722-724.  Back to cited text no. 93
    
94.Duffy SJ, Gokce N, Holbrook M, Huang A, Frei B, Keaney JF, Vita JA. Treatment of hypertension with ascorbic acid. Lancet 1999;354:2048-2049.  Back to cited text no. 94
    
95.Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. . Am J Clin Nutr 2006; 83(4):754-759.  Back to cited text no. 95
    
96.Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. Vitamin D: A negative endocrine regulator of the rennin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol 2004;89-90(1-5):387-392.  Back to cited text no. 96
    
97.Myers J. Exercise and Cardiovascular Health. Circulation 2003;107:e2.   Back to cited text no. 97
    
98.Baliga RR, Narula J. Salt Never Calls Itself Sweet. Indian J Med Res 2009;129:472-477.  Back to cited text no. 98
[PUBMED]  Medknow Journal  
99.Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O'Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr 2005;81:341-354.  Back to cited text no. 99
    
100.Schneider RH, Alexander CN, Staggers F, Rainforth M, Salerno JW, Hartz A, Arndt S, Barnes VA, Nidich SI. Long-Term Effects of Stress Reduction on Mortality in Persons >55 Years of Age With Systemic Hypertension. Am J Cardiol 2005;95:1060-1064.   Back to cited text no. 100
    
101.Cysarz D, Bussing A. Cardiorespiratory synchronization during Zen meditation. Eur J Appl Physiol 2005;95:88-95.   Back to cited text no. 101
    
102.Batey DM, Kaufmann PG, Raczynski JM, Hollis JF, Murphy JK, Rosner B, Corrgan SA, Rappaport NB, Danielson EM, Lasser NL, Kuhn CM. Stress management intervention for primary prevention of hypertension: detailed results from Phase I trials of Hypertension Prevention (TOHP-I). Ann Epidemiol 2000; 10(1):45-58.  Back to cited text no. 102
    
103.Bennett P, Wallace L, Carroll D, Smith N. Treating Type A behaviours and mild hypertension in middle-aged men. J Psychosom Res 1991; 35:209-223.  Back to cited text no. 103
    
104.Linden W, Lenz JW, Con AH. Individualized stress management for primary hypertension: a randomized trial. Arch Intern Med 2001;161:1071-1080.  Back to cited text no. 104
    
105.Ellis BJ, Essex MJ. Family Environments, Adrenarche, and Sexual Maturation: A Longitudinal Test of a Life History Model. Child Development 2007; 78(6):1799-1817.  Back to cited text no. 105
    
106.Green AL, Wang S, Owen SLF, Paterson DJ, Stein JF, Aziz TZ, Dodge CJ, Mayberg MR, Grossman RG. Controlling the heart via the brain: a potential new therapy for orthostatic hypotension. Neurosurgery 2006;58(6):1176-1183.  Back to cited text no. 106
    
107.Green AL, Wang S, Bittar RG, Owen SLF, Paterson DJ, Stein JF, Nain PG, Shlugman D, Aziz TZ. Deep brain stimulation: a new treatment for hypertension? J Clin Neurosci 2007;14(6):592-595.  Back to cited text no. 107
    
108.Bessman AN. Blue-Yellow Vision Deficits in Patients With Diabetes. West J Med 1987;146(4):431-433.  Back to cited text no. 108
    
109.Erb C, Voelker W, Adler M, Wohlrab M, Zrenner E. Color-vision disturbances in patients with coronary artery disease. Color Res Appl 2009;26(S1): S288-291.  Back to cited text no. 109
    
110.Tsivgoulis G, Alexandrov AV, Wadley VG, Unverzagt FW, Go RCP, Moy CS, Kissela B, Howard G. Association of higher diastolic blood pressure levels with cognitive impairment. Neurology 2009; 73:589-595.   Back to cited text no. 110
    
111.Vogels RLC, Scheltens P, Schroeder-Tanka JM, Weinstein HC. Cognitive impairment in heart failure: A systematic review of the literature. Eur J Heart Fail 2007;9:440-449.   Back to cited text no. 111
    
112.Riegel B, Bennett JA, Davis A, Carlson B, Montague J, Robin H, Glaser D. Cognitive Impairment in Heart Failure: Issues of Measurement and Etiology. Am J Crit Care 2002;11:520-528.   Back to cited text no. 112
    
113.Staniforth AD, Kinnear WJM, Cowley AJ . Cognitive impairment in heart failure with Cheyne-Stokes respiration. Heart 2001;85:18-22.  Back to cited text no. 113
    
114.Elias PK, Elias MF, Robbins MA, Budge MM, Staessen JA, Birkenhager WH. Blood pressure-related cognitive decline: Does age make a difference? Commentary. Hypertension 2004; 44(5):612-613/631-636.   Back to cited text no. 114
    
115.Gunstad J, Paul RH, Cohen RA, Tate DF, Gordon E. Obesity is associated with memory deficits in young and middle-aged adults. Eat Weight Disord 2006; 11(1):e15-9.  Back to cited text no. 115
    
116.Eftekhari H, Uretsky S, Messerli F. Blood pressure, cognitive dysfunction, and dementia. J Am Soc Hypertens 2007;1(2):135-144.  Back to cited text no. 116
    
117.Moretti R, Torre P, Antonello RM, Manganaro D, Vilotti C, Pizzolato G. Risk factors for vascular dementia: Hypotension as a key point. Vasc Health Risk Manag 2008;4(2):395-402.  Back to cited text no. 117
    
118.Gates CA, Cobb JL, D'Agnostino RP, Wolp PA. The relation of Hearing in the Elderly to the presence of cardiovascular disease and cardiovascular risk factors. Arch Otolaryngol Head Neck Surg 1993; 119: 159-161.  Back to cited text no. 118
    
119.Drettner B, Hedstrand H, Klockhoff I. Cardiovascular risk factors and Hearing Loss. Acta Otolaryngol 1975;79:366-371.  Back to cited text no. 119
    
120.Devore P. Prevalence of Olfactory Dysfunction, Hearing Deficit, and Cognitive Dysfunction Among Elderly Patients in a Suburban Family Practice. South Med J 1992;85(9):894-896.  Back to cited text no. 120
    
121.Kandel E. The New Science of Mind. Scientific American Mind 2006;17(2):62-69.   Back to cited text no. 121
    
122.Grakov IG. Strannik Diagnostic and Treatment System: a Virtual Scanner for the Health Service. Minutes of Meeting No. 11 of the Praesidium of the Siberian of the Academy of Medical Sciences of the USSR (AMN) 4 December 1985.  Back to cited text no. 122
    
123.Kostoglou-Athanassiou I, Treacher DF, Wheeler MJ, Forsling ML. Bright light exposure and pituitary hormone secretion. Clin Endocrinol 1998; 48(1):73-79.  Back to cited text no. 123
    
124.Barcroft J, Nisimaru Y, Puri SR. The Action of the Splanchic Nerves on the Spleen. J Physiol 1932; 74(3):321-326.  Back to cited text no. 124
    
125.Bartter FC, Delea CS, Kawasaki T, Gill JR. The adrenal cortex and the kidney. Kidney Int 1974;6:272-280.   Back to cited text no. 125
    
126.Zhang W, Chung CS, Riordan MM, Wu Y, Shmuylovich L, Kovács SJ. The Kinematic Filling Efficiency Index of the Left Ventricle: Contrasting Normal vs. Diabetic Physiology. Ultrasound Med Biol 2007;33(6):842-850.  Back to cited text no. 126
    
127.Rath M, Pauling L. Hypothesis: lipoprotein(a) is a surrogate for ascorbate. Proc Natl Acad Sci USA.1990;87(16):6204-6207.  Back to cited text no. 127
    
128.Crowell RM, Olsson Y. Impaired microvascular filling after focal cerebral ischaemia in monkeys. Neurology 1972; 22:500-504.  Back to cited text no. 128
    
129.Brown M, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Sci Am 1984;251:58-56.  Back to cited text no. 129
    
130.Ravnskov U. Is atherosclerosis caused by high cholesterol? Q J Med 2002;95:397-403.  Back to cited text no. 130
    
131.Granaat D. The spleen in the regulation of the arterial blood pressure. J Physiol 1953; 122(2):209-219.  Back to cited text no. 131
    
132.Klopper PJ. The influence of the spleen on the blood pressure in the portal vein. Ned Tijdschr Geneeskd 1958; 102(36):1774-1776.  Back to cited text no. 132
    
133.Romanovsky AA, Petersen SR. The spleen: another mystery about its function. Am J Physiol Regulatory Integrative Comp Physiol 2003; 284(6): R1378-R1379.  Back to cited text no. 133
    
134.Andrew P, Deng Y, Kaufman S. Fluid extravasation from spleen reduces blood volume in endotoxemia. Am J Physiol Regulatory Integrative Comp Physiol 2000; 278:R60-R65.  Back to cited text no. 134
    
135.Kaufman S, Levasseur J. Effect of portal hypertension on splenic blood flow, intrasplenic extravasation and systemic blood pressure. Am J Physiol Regulatory Integrative Comp. Physiol 2003; 284(6): R1580-R1585.  Back to cited text no. 135
    
136.Andrew PS, Deng Y, Sultanian R, Kaufman S. Nitric oxide increases fluid extravasation from the splenic circulation of the rat. Am J Physiol Regulatory Integrative Comp Physiol 2001;280(4):R959-R967.  Back to cited text no. 136
    
137.Hamza SM, Kaufman S. Role of spleen in integrated control of splanchnic vascular tone: physiology and pathophysiology. Can J Physiol Pharmacol 2009; 87(1): 1-7.   Back to cited text no. 137
    
138.Deng Y, Kaufman S. Splenorenal Reflex Regulation of Arterial Pressure. Hypertension 2001;38:348.  Back to cited text no. 138
    
139.Legramante JM, Galante A. Sleep and Hypertension. A Challenge for the Autonomic Regulation of the Cardiovascular System. Circulation 2005;112:786-788.   Back to cited text no. 139
    
140.Kuo TB, Yang CCH. Sleep-related changes in cardiovascular neural regulation in spontaneously hypertensive rats. Circulation 2005;112:849-854.  Back to cited text no. 140
    
141.Kato M, Phillips BG, Sigurdsson G, Narkiewicz K, Pesek CA, Somers VK. Effects of sleep deprivation on neural circulatory control. Hypertension 2000; 35: 1173-1175.  Back to cited text no. 141
    
142.Hall SAA, Shackelton RA, Rosen RCA, Araujo ABA. Sexual Activity, Erectile Dysfunction, and Incident Cardiovascular Events. Am C Cardiology 2010; 105(2): 192-197.  Back to cited text no. 142
    
143.Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA 2003; 290: 1906-1914.  Back to cited text no. 143
    
144.Golden SH, Williams JE, Ford DE, Yeh H-C, Paton SC, Nieto FJ, Brancati FL. Anger temperament is modestly associated with the risk of type 2 diabetes mellitus: The atheroslcerosis risk in communities study. Psychoneuroendocrinology 2006; 31(3): 325-332.   Back to cited text no. 144
    
145.Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-234.  Back to cited text no. 145
    
146.Stranges S, Dorn JM, Donahue RP, Browne RW, Freudenheim JL, Hovey KM, Trevisan M. Oxidation, type 2 diabetes and coronary heart disease, a complex interaction. Findings from a population-based study. Diabetes Care 2008;31(9):1-3.   Back to cited text no. 146
    
147.Borghouts LB, Keizer HA. Exercise and insulin sensitivity: a review. Int J Sports Med 2000; 21(1): 1-12.  Back to cited text no. 147
    
148.Iliescu EA, Yeates KE, Holland DC. Quality of sleep in patients with chronic kidney disease. Nephrol Dial Transplant 2004;19:95-99  Back to cited text no. 148
    
149.Padh H. Cellular functions of ascorbic acid. Biochem Cell Biol1990;68:1166-1173.  Back to cited text no. 149
    
150.Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and mortality among a sample of the United States population. Epidemiology 1992;3:194-202.  Back to cited text no. 150
    
151.Wattanakit K, Coresh J, Muntner P, Marsh J, Folsom AR. Cardiovascular risk among adults with chronic kidney disease, with or without prior myocardial infarction. J Am Coll Cardiol 2006;48(6):1183-1189.  Back to cited text no. 151
    
152.Parikh NI, Hwang S-J, Larson MG, Levy D, Fox CS. Chronic Kidney Disease as a Predictor of Cardiovascular Disease (From the Framingham Heart Study). Am J Cardiol 2008;102(1):47-53.  Back to cited text no. 152
    
153.Agarwal R, Nissenson AR, Batlle D, Coyne DW, Trout JR, Warnock DG. Prevalence, treatment, and control of hypertension in chronic hemodialysis patients in the United States. Am J Med 2003; 115: 291-297.  Back to cited text no. 153
    
154.Rowe WJ. Extraordinary Hypertension after a Lunar Mission. Am J Med 2009;122(11):e1.   Back to cited text no. 154
    
155.Kestenbaum B, Rudser KD, de Boer IH, Peralta CA, Fried LF, Shlipak MG, Palmas W, Stehman-Breen C, Siscovick DS. Differences in Kidney Function and Incident Hypertension: The Multi-Ethnic Study of Atherosclerosis. Ann Intern Med 2008;148:501-508.  Back to cited text no. 155
    
156.Goldin RM. Hypertension and CKD. Kidney Beginnings: The Magazine 2005;4(1) (Accessed June 11, 2010, at http: //www. aakp.org/aakp-library/hypertension-and-c-k-d/).  Back to cited text no. 156
    
157.Mouw DR, Sullo EJ. What are the causes of hypomagnesemia? J Fam Pract 2005;54(2):174-176.  Back to cited text no. 157
    
158.Tubek S. Role of zinc in regulation of arterial blood pressure and in the etiopathogenesis of arterial hypertension. Biol Trace Elem Res 2007; 117 (1-3): 39-51.  Back to cited text no. 158
    
159.Kausz AT, Steinberg EP, Nissenson AR, Pereira BJG. Prevalence and Management of Anemia Among Patients with Chronic Kidney Disease in a Health Maintenance Organization. Dis Manage Health Outcomes 2002; 10:505-513.  Back to cited text no. 159
    
160.Lichodziejewska B, Klos B, Rezler J, Grudzka K, Dluzniewska M, Budaj A, Ceremuzynski L. Clinical symptoms of mitral valve prolapse are related to hypomagnesemia and attenuated by magnesium supplementation. Am J Cardiology 1997; 79 (6): 768-772.  Back to cited text no. 160
    
161.Kitlinski M, Stepniewski M, Nessler J, Konduracka E, Solarska K, Piwowarska W, Erhardt L. Is magnesium deficit in lymphocytes a part of the mitral valve prolapse syndrome? Magnesium Res 2004; 17 (1): 39-45.  Back to cited text no. 161
    
162.Shechter M, Sharir M, Labrador MJ, Forrester J, Silver B, Bairey D, Merz CN. Oral magnesium therapy improves endothelial function in patients with coronary artery disease. Circulation 2000; 102: 2353-2358.  Back to cited text no. 162
    
163.Jee SH, Miller ER, Guallar E, Singh VK, Appel LJ, Klag MJ. The effect of magnesium supplementation on blood pressure: a meta-analysis of randomized clinical trials. Am J Hypertens 2002;15(8):691-696.  Back to cited text no. 163
    
164.Zehender M, Meinertz T, Faber T, Caspary A, Jeron A, Bremm K, Just H. Antiarrhythmic effects of increasing the daily intake of magnesium and potassium in patients with frequent ventricular arrhythmias. J Am Coll Cardiol 1997;29:1028-1034.  Back to cited text no. 164
    
165.Gottlieb SS. Importance of magnesium in congestive heart failure. Am J Cardiol 1989;63:39G-42G.  Back to cited text no. 165
    
166.Walti MK, Zimmermann MB, Spinas GA, Hurrell RF. Low plasma Magnesium in type 2 Diabetes. Swiss Med Wkly 2003;133:289-292.  Back to cited text no. 166
    
167.Sjogren A, Floren CH, Nilsson A. Magnesium, potassium and zinc deficiency in subjects with type II diabetes mellitus. Acta Med Scand 1988; 224: 461-466.  Back to cited text no. 167
    
168.Velioglu SK, Ozmenoglu M. Migraine-related seizures in an epileptic population. Cephalalgia 1999; 19 (9):797-801.  Back to cited text no. 168
    
169.Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatology 1995; 22(5):953-958.  Back to cited text no. 169
    
170.Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium therapy for children with moderate to severe acute asthma. Arch Pediatr Adolesc Med 2000;154(10)979-983.  Back to cited text no. 170
    
171.Wilens TE, Biederman J, Spencer TJ, Frazier J, Prince J, Bostic J, Rater M, Soriano J, Hatch M, Sienna M, Millstein RB, Abrantes A. Controlled High Doses of Pemoline for adults with attention deficit/hyperactivity disorder. J Clin Psychopharmacology 1999;19(3):257-264.  Back to cited text no. 171
    
172.Starobrat-Hermelin B. The effect of deficiency of selected bioelements on hyperactivity in children with certain specified mental disorders. Ann Acad Med Stetin 1998;44:297-314.  Back to cited text no. 172
    
173.Idogun SE, Imarengiaye CO, Momoh SM. Extracellular Calcium and Magnesium in Pre-eclampsia and Eclampsia. Afr J Reprod Health 2007; 11(2):89-94.  Back to cited text no. 173
    
174.Mildred S. Seelig. Consequences of Magnesium Deficiency on the Enhancement of Stress Reactions; Preventive and Therapeutic Implications (A Review). J Am Coll Nutr 1994;13(5):429-446.  Back to cited text no. 174
    
175.Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP. Colas but not other carbonated beverages are associated with low bone density in older women. The Framingham Osteoporosis Study. Am J Clin Nut 2006;84(4):936-942.  Back to cited text no. 175
    
176.Saldana TM, Basso O, Darden R, Sandler DP. Carbonated beverages and chronic kidney disease. Epidemiology 2007;18(4):501-506.  Back to cited text no. 176
    
177.Ewing GW, Ewing EN. 'Virtual Scanning - a new generation of medical technology - beyond biomedicine?' ISBN 978-0-9556213-0-7 pub Montague Healthcare books.  Back to cited text no. 177
    
178.Gao J-H, Parsons LM, Bower JM, Xiong J, Li J, Fox PT. Cerebellum implicated in sensory acquisition and discrimination rather than motor control. Science 1996:272 (5261):545-547.  Back to cited text no. 178
    
179.Malliani A, Pagani M, Lombardi F, Cerutti S. Cardiovascular neural regulation explored in the frequency domain. Circulation 1991;84(2):482-492.  Back to cited text no. 179
    
180.Montano N, Porta A, Cogliati C, Costantino G, Tobaldini E, Casali KR, Iellamo F. Heart rate variability explored in the frequency domain: a tool to investigate the link between heart and behavior. NeuroSci. Biobehaviour Rev 2009;33(2):71-80.  Back to cited text no. 180
    
181.Osborn JW, Jacob F. Guzman P. A neural set point for the long-term control of arterial pressure: beyond the arterial baroreceptor reflex. Am J Physiol Regul Integr Comp Physiol 2005;288(4): R846-55.  Back to cited text no. 181
    
182.Jacob F, Ariza P, Osborn JW. Renal denervation chronically lowers arterial pressure independent of dietary sodium intake in normal rats. Am J Physiol Heart Circ Physiol 2003;284(6):H2302-H2310.  Back to cited text no. 182
    
183.Guyton AC. Blood pressure control - special role of the kidneys and body fluids. Science 1991;252:1813.  Back to cited text no. 183
    



 
 
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