Formal Analysis of Mechanisms Increasing Arterial Pressure
Предложено расширенное представление о механизмах регуляции среднего артериального давления в норме и при артериальной гипертонии. У позвоночных (в частности, у человека) есть многомасштабная энергетическая мегасистема, ведущая борьбу против продолжительной нехватки АТФ в клетках. Механизмы, баланси...
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Міжнародний науково-навчальний центр інформаційних технологій і систем НАН України та МОН України
2014
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irk-123456789-845262015-07-10T03:02:20Z Formal Analysis of Mechanisms Increasing Arterial Pressure Grygoryan, R.D. Медицинская и биологическая кибернетика Предложено расширенное представление о механизмах регуляции среднего артериального давления в норме и при артериальной гипертонии. У позвоночных (в частности, у человека) есть многомасштабная энергетическая мегасистема, ведущая борьбу против продолжительной нехватки АТФ в клетках. Механизмы, балансирующие скорости производства и расхода АТФ в каждой клетке, находятся во взаимосвязи с механизмами и вегетативными системами организменного масштаба. Развитие артериальной гипертонии скорее является компенсаторной реакцией на нехватку энергии, чем болезнью. Запропоновано розширене уявлення про механізми регуляції середнього артеріального тиску в нормі та при артеріальній гіпертонії. У хребетних (зокрема, у людини) є багатомасштабна енергетична мегасистема, яка веде боротьбу проти тривалої нестачі АТФ в клітинах. Механізми, які балансують швидкості продукування та використання АТФ в кожній клітині, находяться у зв’язку з механізмами та вегетативними системами організму. Розвиток артеріальної гіперт The purpose of the paper is to propose an extended view of mechanisms regulating long-term level of mean arterial pressure (MAP). 2014 Article Formal Analysis of Mechanisms Increasing Arterial Pressure / R.D. Grygoryan // Кибернетика и вычислительная техника. — 2014. — Вип. 177. — С. 68-78. — Бібліогр.: 16 назв. — англ. 0452-9910 http://dspace.nbuv.gov.ua/handle/123456789/84526 519.6+612 en Кибернетика и вычислительная техника Міжнародний науково-навчальний центр інформаційних технологій і систем НАН України та МОН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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Медицинская и биологическая кибернетика Медицинская и биологическая кибернетика |
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Медицинская и биологическая кибернетика Медицинская и биологическая кибернетика Grygoryan, R.D. Formal Analysis of Mechanisms Increasing Arterial Pressure Кибернетика и вычислительная техника |
| description |
Предложено расширенное представление о механизмах регуляции среднего артериального давления в норме и при артериальной гипертонии. У позвоночных (в частности, у человека) есть многомасштабная энергетическая мегасистема, ведущая борьбу против продолжительной нехватки АТФ в клетках. Механизмы, балансирующие скорости производства и расхода АТФ в каждой клетке, находятся во взаимосвязи с механизмами и вегетативными системами организменного масштаба. Развитие артериальной гипертонии скорее является компенсаторной реакцией на нехватку энергии, чем болезнью. |
| format |
Article |
| author |
Grygoryan, R.D. |
| author_facet |
Grygoryan, R.D. |
| author_sort |
Grygoryan, R.D. |
| title |
Formal Analysis of Mechanisms Increasing Arterial Pressure |
| title_short |
Formal Analysis of Mechanisms Increasing Arterial Pressure |
| title_full |
Formal Analysis of Mechanisms Increasing Arterial Pressure |
| title_fullStr |
Formal Analysis of Mechanisms Increasing Arterial Pressure |
| title_full_unstemmed |
Formal Analysis of Mechanisms Increasing Arterial Pressure |
| title_sort |
formal analysis of mechanisms increasing arterial pressure |
| publisher |
Міжнародний науково-навчальний центр інформаційних технологій і систем НАН України та МОН України |
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2014 |
| topic_facet |
Медицинская и биологическая кибернетика |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/84526 |
| citation_txt |
Formal Analysis of Mechanisms Increasing Arterial Pressure / R.D. Grygoryan // Кибернетика и вычислительная техника. — 2014. — Вип. 177. — С. 68-78. — Бібліогр.: 16 назв. — англ. |
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Кибернетика и вычислительная техника |
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2025-07-06T11:35:19Z |
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1836897244759982080 |
| fulltext |
68
Медицинская и биологическая
кибернетика
УДК 519.6+612
A FORMAL ANALYSIS OF MECHANISMS
INCREASING ARTERIAL PRESSURE
Grygoryan R.D.
Institute of Software Systems of National Academy of Sciences of Ukraine
Предложено расширенное представление о механизмах
регуляции среднего артериального давления в норме и при артериальной
гипертонии. У позвоночных (в частности, у человека) есть
многомасштабная энергетическая мегасистема, ведущая борьбу против
продолжительной нехватки АТФ в клетках. Механизмы, балансирующие
скорости производства и расхода АТФ в каждой клетке, находятся во
взаимосвязи с механизмами и вегетативными системами организменного
масштаба. Развитие артериальной гипертонии скорее является
компенсаторной реакцией на нехватку энергии, чем болезнью.
Ключевые слова: артериальная гипертония, энергетика,
физиология кровообращения, модели.
Запропоновано розширене уявлення про механізми
регуляції середнього артеріального тиску в нормі та при артеріальній
гіпертонії. У хребетних (зокрема, у людини) є багатомасштабна
енергетична мегасистема, яка веде боротьбу проти тривалої нестачі АТФ в
клітинах. Механізми, які балансують швидкості продукування та
використання АТФ в кожній клітині, находяться у зв’язку з механізмами
та вегетативними системами організму. Розвиток артеріальної гіпертонії
скоріше є компенсаторною реакцією на нестачу енергії, ніж хворобою.
Ключові слова: артеріальна гіпертонія, енергетика,
фізіологія кровообігу, моделі.
INTRODUCTION
Arterial hypertension (AH) is a multi-factor disease mostly developing
gradually [1, 2]. About 30% of adults are affected by AH. However, its etiology is
clear only for 5% of diseased people [3]. AH eventually leads to associated serious
pathologies (heart failure, brain hemorrhagic stroke, renal diseases) [2–5]. In fact,
therapies of AH are often aimed rather to mitigate its symptoms than really
eliminate the disease [3]. Despite advanced drugs and cure, the number of diseased
people is not reducing [3]. Experts recognize that there are still some cases of
essential AH uncovered by its theories [2, 5, 6]. This disappointment gives a reason
to suspect that our knowledge of physiological mechanisms responsible for a
homeostasis of arterial pressure (AP) contains serious gaps. Naturally,
mathematical models of AP’s physiological control could not be free of these gaps.
To come to most comprehensive models, we need to extend our understanding of a
role playing by cardiovascular system (CVS) in human organism. The extended
view of CVS must include both CVS’s autonomous control mechanisms and
Р.Д. Григорян, 2014
ISSN 0452-9910. Кибернетика и вычисл. техника. 2014. Вып. 177
69
conditions in which functions of these mechanisms become modulated via factors
born out of CVS.
This article has two goals. The fist one — theoretical goal is to provide special
formalized analysis determining both mechanisms of normal AP and causes of its
changes. The second one — medical goal is to facilitate a search for cardinal
curing of AH.
BASIC INFORMATION
Most theories of AP’s homeostasis silently assume that a stabilization of mean
arterial pressure (MAP) is the goal of control mechanisms [4–6]. In frame of this
concept, alterations of MAP are interpreted as undesirable aberrations of CVS. In
particular, AH is considered as a disease that should be cured in ways leading to
normalization of MAP (or its end-systolic and end-diastolic peaks).
A cardinally new view of AP’s role in organism is proposed in recent general
theory of reversible adaptation [7–9]. In fact, the conceptual leap concerns both
AP’s role and fundamentals of organs integration for providing of vegetative
functions. To mostly relief represent the new concept, it is useful to compare it
with a traditional concept.
In traditional physiology, every organ is considered to be an upper-scale
structure that has its specialized function(s) and autonomous control systems.
Under environmental violations, these organs and systems generally provide
organism’s homeostasis. In contrast, the energy concept showed that a group of
upper-scale organs, direct or indirectly involved in modulation of cell’s mean rate
of ATP-production, form an exclusive functional system aimed to provide of long-
term energy balance (EB) in every specialized cell of the organism. This functional
system was called an energy megasystem (EMS) because of its enormously large
size and complexity. It is important to remember that the CVS is one of constituent
systems of EMS thus a functional activity of CVS is reciprocally associated with
the activity of remained structures of EMS.
In human cells, ATP is produced both via anaerobe glycolisis in cytoplasm
and via oxygenation of pyruvic acid in mitochondria. The pyruvate is a common
chemical output of intracellular transformations of carbohydrates, fatty acids, fats,
and proteins. Normally, mitochondria are main producers of ATP. As the aerobic
cell does not store a large amount of ATP-molecules, their mean mitochondrial
synthesis rate ( sv ) is tightly associated with a mean rate ( dv ) of dissociation of
ATP. Although intracellular mechanisms balancing sv with dv are known, because
of limited efficiency, under chronic increase of dv , these mechanisms do not
provide long-term EB.
The energy view on human physiology revealed several hidden internal
relationships of organs and systems. Most of these relationships was evolutionary
saved because they accelerate cells’ fight against chronic energy deficit [7]. Indeed,
the long-term lack of ATP suppresses most cellular activities including cell’s and
entire organism’s reactivity to dangerous environmental challenges. So, in
conditions of unstable environment, those multicellular organisms that accelerated
mitochondrial enlargement in inhibited cells, had more chances to survive. It is
Р.Д. Григорян, 2014
ISSN 0452-9910. Кибернетика и вычисл. техника. 2014. Вып. 177
70
reasonable to state that such a type of organism is the energetically most advanced.
In human cells, molecules of ATP are main consumables. Both the
metabolism and the reactivity of every cell are vulnerable to deficit of ATP. A lack
of energy suppresses or interrupts several biochemical transformations and affects
cellular reactivity to extracellular signals. So, even under rest conditions, a
functional integrity of entire organism or its physiological systems critically
depends upon compensatory incomes of consumables necessary for a synthesis of
ATP.
Mitochondrial total surface is main long-term determiner of sv [7]. Under
continuous situation of ds vv 1< , eventually an energy deficit will appear. So,
cytoplasm concentrations of various interim chemicals eventually elevate. Some of
these chemicals (e.g., hypoxia inducible factors [2]) increase sv and activate
mechanisms of proliferation/hypertrophy of mitochondrion. Theoretically, this
negative feedback should work until a new rate of ATP production ( ds vv 11 ≥ )
eliminates the deficit of energy. In real conditions, the mitochondrial up-build
requires appropriate material incomes.
The aerobic cell cannot store a large numbers of ATP molecules, thus the
increased sv automatically decreases the number of consumables (carbohydrates
and oxygen). There are multiple mechanisms compensating this lack of
consumables. Under local (regional) deficit of either oxygen or glucose, local
vasodilatation (provided by chemicals leaved suffering cells) does increase blood
flow and compensate the moderate lack of incomes. However, in case of a large
affected region, the regional vasodilatation drops MAP and decreases blood flows.
There are several ways to overcome such energy problems. An increase of MAP is
a way leading to elimination of a severe deficit of ATP only in case of sufficient
blood concentrations of glucose and oxygen. In case of low glucose, special low
molecular chemicals produced by energy suffered cells activate mechanisms of
glucose neogenesis from liver glycogen.
There are three subways for compensating of low blood oxygen. A
mobilization of blood from its depots is the first and most rapid way but this way
has very limited resource. An increase of lung ventilation is the second rapid way
supporting blood erythrocytes’ oxygenation. At last, an increase of a rate of
erythropoiesis is the main but inertial way capable to provide additional
erythrocytes for transporting of oxygen toward cells. These mechanisms all
together prompt every cell to overcome its energy problems if only the organism
possesses sufficient internal material resources. In versus case, these materials have
to be taken from outside therefore, those behaviors that are integrated in food
search and assimilation are also involved in EMS.
This general view of organism’s mechanisms, evolutionary saved for optimal
fighting of energy deficit in cells, is the basis for comprehending of causes and
mechanisms for both fluctuations and long-term shifts of MAP. To facilitate this
comprehension and to create a basis for advanced mathematical models, let us
formalize current physiological knowledge concerning neural-hormonal control of
MAP.
Р.Д. Григорян, 2014
ISSN 0452-9910. Кибернетика и вычисл. техника. 2014. Вып. 177
71
A FORMAL DESCRIPTION OF MECHANISMS REGULATING MAP
Assume )(tPA and )(tPV denote momentum values of AP and central venous
pressure appropriately. In practice, physicians use AP’s two characteristics: end-
systolic and end-diastolic peaks. But these extreme values of )(tPA depend on
measurement site on arterial tree. Besides, for a given time τ , a mean blood flow
between every two vascular segments is determined by their mean pressure
gradients. Usually, τ represents the duration of a cardiac cycle. To calculate
cardiac output )(τQ , one needs mean value of total peripheral resistance )(τTR , as
well as mean values )(tP A , )(tPV of )(tPA , and )(tPV respectively.
∫
τ
τ
=
0
)(1)( dttPtP AA ; ∫
τ
τ
=
0
)(1)( dttPtP VV ; )(/))()(()( τ−=τ TVA RtPtPQ .
To clarify common and specific mechanisms fluctuating human hemodynamic
characteristics, as well as to determine distinguish signs of these mechanisms in
comparison with mechanisms shifting both )(tP A and )(tPA , we must remember
that the CVS is an open non-stationary system. Fluctuations of )(tPA and )(tP A in
physiological conditions suggest that characteristics of CVS are time-variables.
Energy-based modulators of )(tP A are not the exclusive external influences on
CVS. Hemodynamic effects of modulators can be realized via changes of limited
number of CVS’s characteristics: )(tQ , vascular tone )(tTv , blood volume )(tVs .
So, every controller of human hemodynamics should have an access at least to one
of parameters that determine )(tQ , )(tTv , and )(tVs .
As )(tP A is in the focus of our analysis, it is worth to stress that )(tP A is
most sensitive to variations of )(tVs . Traditionally, kidneys are assumed to be
main regulator of )(tVs . Indeed, under dropping of )(tP A , cells of juxtaglomerular
complex release renin that go to circulate. In liver cells, renin causes a release of
angiotensin I (non-active protein). After a lung circulation, the angiotensin I is
transforming into an angiotensin II which is a vasoconstrictor increasing )(tP A .
Besides, angiotensin II compels special cells to produce a hormone aldosterone. In
renal tubules, aldosterone increases a fluid reabsorption rate. Totally, these
endogenous chemical agents increase )(tP A via increasing of both )(tVs and )(tQ
[5, 7].
In frame of this concept, there is assumed to be none interim alteration
between the decrease of )(tP A and decrease of filtration rate in juxtaglomerular
cells thus, the rennin-angiotensin system is considered to be a regulator of )(tVs .
This concept could be true in case of absolutely passive filtration in renal capsules.
In case the filtration is at least a partially active process provided by ATP, there
will be a time delay between a drop of pressure in renal arterioles and release of
renin. Indirectly, this supposes that a dependence of renin from )(tP A is rather
Р.Д. Григорян, 2014
ISSN 0452-9910. Кибернетика и вычисл. техника. 2014. Вып. 177
72
associative than causal. This qualification, seeming to be secondary, is crucial in
frame of energy concept of arterial pressure. The fact that currently nine versions
of angiotensines (with unclear contributions in hemodynamic shifts) are discovered
gives additional reason for revising of traditional view on renal control of )(tVs
and )(tP A [5, 6]. It was supposed that renin or its functional analogues are
universal indicators of energy lack in cells of different specialization [8].
So, practically all our specialized cells take part in determining of CVS’s state
and a value of )(tP A . This is the essence of novel energy concept of AH’s etiology
[7, 8]. A brief description of this concept given below is to facilitate understanding
of main intracellular and upper-scales mechanisms responsible for both
fluctuations and long-term shifts of )(tP A .
Under given central venous pressure, )(tQ depends on heart rate )(tF an
ejection fraction (EF). Under constant total peripheral resistance, EF can be
characterized by a coefficient )(tk calculated as a quotient of stroke volume of
ventricle to its end-diastolic volume [7].
The integral vascular tone )(tTv reflects values of arterial and venous
unstressed volumes )(tU A , )(tUV and volumetric rigidities )(tDA , )(tDV
respectively. In every vascular compartment, its vascular resistance )(tRv depends
on )(tV , )(tU , and )(tD [8]. An exact formula connecting these characteristics of
CVS with )(tPa hardly can be identified but a large amount of successive
mathematical models are based on approximations like
))(),(),(),(),(),(()( tktFtRtTtUtVtP vvssA Ψ≈ . (1)
For convenience, CVS’s characteristics included in Ψ – function in (1),
further are denoted ix .
))(()( txtP iA Ψ≈ . (2)
Assume )0(ix is a value of every variable ix under unstressed regulators. In
every other physiological state, and for every t , variables )(txi represent regulator
alterations of the )0(ix on )(txi∆ . Every )(txi∆ has its extreme values, so
Ext
i i
xtx ≤∆ )( . Within this interval, the value of )(txi∆ can be calculated as an
algebraic sum of effects, caused by mj ,1= physiochemical influences. For a part
of such influences, their sources are known (baroreflector, chemoreflector
influences, descending nervous influences of brain upper structures, and a variety
of humoral agents). Another group of influences (e.g., temperature, metabolic,
exogenous activators or inhibitors) can have mainly local effects (e.g., modulating
only the basic rate of heart pacemakers). A formal description of these
opportunities looks as:
Р.Д. Григорян, 2014
ISSN 0452-9910. Кибернетика и вычисл. техника. 2014. Вып. 177
73
>
∆=∆≤∆±
=
∑
=
Ext
ii
Ext
i
m
r
iri
Ext
iiii
i
xtxx
txtxxtxtxx
tx
)(,
,)()(where,)(),()0(
)( 1 (3)
where
≥∆
<<+−
≤
=∆
s
irir
s
ir
s
iriririeiririr
irir
ir
YtYx
YtYybytYa
ytY
tx
)(,
)(,))((
)(,0
)( . (4)
A piecewise linear relations (4) commonly represent characteristics of
specialized receptors. The formula (4) tooks into account that every such receptor
is not active until its activity threshold iry had been overcome. The formula (4)
also supposed that every receptor has its saturation level s
irY . Within these extreme
values s
iririr YtYy << )( , the receptor activity )(tYir is proportional to an over-
threshold value of real biological variable (e.g., blood transmural pressure or
chemical parameters). Certainly, this linear approximation does not cover the entire
diapason of receptors’ activity. Nevertheless, the reduced formulas (3) and (4) are
capable to model main cardiovascular reflector responses irx∆ to internal/external
challenges of moderate values characteristic for physiological conditions. For
every receptor, the sensitivity coefficient ira is considered to be constant for the
entire diapason of receptor function. It is assumed that the summands ieb are not
zero only for those ix that surely are under additional influences.
Formalizations (3) and (4) cover every variable of CVS. However, the
multiple control of the hemodynamics has several nuances that should be special
commented. To accentuate some of these nuances, it is useful to compare the
control of the heart pump function with the control of regional vascular tones. Let
us look inside the control of )(tF .
It is known that under normal physiological conditions, the rate of right
atrium’s pacemakers is the main determiner of )(tF . From the other hand, the
pacemakers are sensitive to changes of both blood temperature )( oT and blood
chemical state )(z . So, the basic rate ( af ) of right atrium’s pacemakers is a
function of at least two independent variables: ),( zTf o
a . Under constz = , the
function ),( zTf o
a is practically linear within C41C33 °≤≤° oT . Under
constT o = , variations of z could either increase af or decrease it.
Descending nervous modulations of )(tF can reach the right atrium’s
pacemakers via appropriate nervous fibers of cardiac sympathetic or
parasympathetic nerves. The sympathetic fibers cause positive chronotropic effect
while the parasympathetic pathways have negative chronotropic effect. Denote
these effects sF∆ and vF∆ respectively. Then, descending modulator effects
Р.Д. Григорян, 2014
ISSN 0452-9910. Кибернетика и вычисл. техника. 2014. Вып. 177
74
caused both by brain supra-bulbar structures and by main hormonal modulators
(adrenalin, noradrenalin, and acetylcholine) can be formalized as
vs
o
a FFzTftF ∆−∆+= ),()( . (5)
Note that the formula (5) is indifferent to nature of modulators. In practice, a
differential diagnosis of AH and its cure require information about investment of
every modulator in a measured alterations of )(tF . This last sentence is explained
below.
Assume, an elevation of )(tPA is caused by an increase of )(tQ . The gain of
)(tQ is possible due to three independent alterations: 1) via increase of )(tPV ;
2) via increase of )(tF ; 3) via increase of heart contractility.
Suppose consttPV =)( . Then nervous alterations either increase the frequency of
sympathetic impulses or decrease the frequency of parasympathetic impulses in the
respective descending heart nervous branches. So, the total effect is in a gain of
)(tQ . In addition, several hormonal agents are also capable to gain of )(tQ .
Indisputable, the therapy of AH should be based on differentiation of these
mechanisms. But even possessing of reliable methods for such differentiation,
there is still one more important problem: it is necessary to clarify the primary
cause of alterations in every regulator mechanism.
The main effect of reflexes activated because of ascending impulses born
in cardiac or arterial mechanoreceptors is to damp cyclic violations
of )(tPA [2, 5, 7]. Chemoreceptor reflexes normally are aimed to increase MAP, as
well as to intensify lung ventilation. Two these alterations commonly provide the
due composition of the arterial blood [5]. As to relative roles of CVS’s nervous and
humoral control mechanisms, researchers agreed only if the discussion concerns
the speed of these mechanisms [2]. Analogically, there is no consensus concerning
roles of a variety of chemicals modulating heart pump function and /or vascular
tone [5]. The last sentence also concerns local effects of low molecular metabolites
(e.g., 22 ,,,,, SONOCOCOOHH −+ ) [2, 3, 12]. So, this ambiguity of thoughts
formed the conceptual relief on which the energy concept of arterial pressure
(ECAP) explained main mechanisms of cardiovascular variability had appeared
[8].
Suppose in (2) some state of arterial pressure )()( * tPtP AA = is already chosen
to be the basic state. In accordance with common concept of homeostasis, the value
of )(* tPA is often close to a special but virtual value )(* tPAN also called as the
normal value of )(tPA under rest. However )(* tPAN is not argued physiologically.
)(* tPAN is statistically calculated as the mean value of )(tPA in a population of
practically healthy people under rest. Thus, )(* tPAN does not mandatorily
represent the normal arterial pressure for an individual. To overcome this
conceptual disparity, recently a concept of individual physiological norm is
proposed [9]. According to the new interpretation, the individual physiological
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norm is a synonymous to organism-scale energy balance. But the energy
production/consumption rates can be balanced on different levels of
ATP-production. This means that instead of an exclusive state of virtual
homeostasis, every organism can have a lot of normal states. Therefore, multiple
combinations of )(txi are capable to provide the values of )(* tPA .
In the dimension of state parameters )(txi of CVS, two states of CVS could
be determined of different )(txi . Although the inequality )0()( ii xtx ≠ appears in
both states, mechanisms responsible for these inequalities are not the same. Indeed,
in one case, the situation of )0()(1 ii xtx ≠ appears because of stressed regulators
while in opposite case of )0()(2 ii xtx ≠ none regulator of CVS is stressed.
Normally, regulator shifts of ix∆ are reversible and do not continue for a long-
time. Besides, such shifts do not cause ultrastructural re-build. However, there is
another type of alterations covering both effectors (myocardium, vascular smooth
muscles) and of regulator mechanisms’ characteristics (activation thresholds,
parameters of the sensitivity and saturation of receptors). Mechanisms responsible
for transitory alterations )0()(1 ii xtx ≠ are known. Moreover, physiologists and
physicians are sure that the alterations have compensatory character. Nevertheless,
both initiator and realizing mechanisms of this goal are still unknown yet. In frame
of the problem of AH, this physiological uncertainty does origin medical problems.
As a rule, most patients addressing for a cure already have signs of a
developed pathology. The multiple regulators of hemodynamics, possible
individual ontogenetic variations of every regulator are factors complicating both a
correct diagnosis of AH and its due cure [3, 13]. Despite these initial problems,
under AH’s extreme cases, the doctor must provide an appropriate cure of AH.
Currently, the cure is aimed to return important characteristics of CVS to their
so-called normal values thus the cure is mostly targeted to elimination of
symptoms [3]. Is such a cure correct? The question is not rhetorical because the so-
called normalization of AH does not take into account the real complexity of EMS
and the multiplicity of individual adaptations [7]. The current medical technologies
are not capable to effectively fight AH via drugs inactivating initial shifts. Thus
AH’s cure displays only transitory effects that are mainly disappearing soon after
the intake of drugs is stopped [3, 5]. From the platform of EMS, such transitory
results evidently show that the cure do not act against new stabile values of )(2 tx i .
In other words, the palliative effect acts only at level of regulators forming )(txi∆ ,
but there is no structural returning to )0(ix .
So, all we know about physiology of CVS concerns its own reflexes aimed to
control AP. The traditional hemodynamic approximation does not point out
determinants of MAP. A search for deep mechanisms indirectly modulating AP,
and likely being associated with functions of other physiological sub-units, could
bring us to an extended concept of AP. During this search, the initial quest is: why
the organism needs AP in general?
According to [6, 7], normally, current level of AP should not be less than a
pressure providing blood flows sufficient for production of due amount of ATP in
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cells. In statics, every cell tries to control its mitochondria for reaching an optimal
summary surface sufficient to balance sv with dv . This balance does not depend
on physiochemical fluctuations in local intercellular environment. In fact, such a
multi-parametric optimization suggests that MAP does properly vary depending on
blood chemical composition. As this composition is resulted of efforts developed
in different physiological sub-systems of EMS, the level of MAP has to be
inversely proportional to activities of mechanisms that regulate blood glucose,
number of erythrocytes, lung ventilation, as well as a concerted function of the
digestive system. This branched system supposes a huge number of situations
satisfying energy needs of cells.
There is one more aspect that should have been analyzed. This aspect concerns
correct understanding of causes transforming the physiological control of AP to its
pathological shifts. Last several years, local rennin-angiotensin systems [6, 10] and
AMP-activated protein kinase [11–16] are in the focus of investigations. At the
moment, experts proposed a lot of hypotheses concerning roles of tissue factors in
control of cardiovascular activity, but practically every hypothesis silently assumes
that there should be some general control of AP. In this paper, another idea based
on casual mutations is provided.
The concept of EMS [7] assumed that the upper-scales sub-units of EMS had
been evolutionary saved because they accelerate the fight of cells against energy
imbalance. An indirect effect of this system is that alterations (geometric sizes,
functional) of sub-units of EMS will be synchronized. Although clinicians had
accumulated a lot of evidences that under certain diseases, a hypertrophy of some
organs (liver, kidneys, heart, and glandules) happened, only the energy concept
explains why and how these alterations correlate.
The evolutionary view of complex regulator ensembles suggests that our
organs and systems are not mandatorily optimal as one could suppose. Although
the anatomy, genetics, and biochemistry provided of many arguments for this
assertion, until recently, analogical physiological arguments were absent. Namely,
the parallelism of efforts developed by a huge number of cells (fighting for
common and scarce resources) is the best argumentation of a thought that the long-
term optimum and the acute-optimum cannot be provided simultaneously [7]. The
upper-scales regulators become activated to create a due productiveness of cell-
scale energy producers – mitochondria. So, the upper-scales regulators are under
chemicals produced by every cell. Perhaps, intravascular endothelial cells,
representing organism’s biggest producer of hormones, play the main role in
modulation of MAP-level. However, the energy concept of AP ensures that the
long-term level of MAP reflects total contribution (including opposite efforts) of
practically all cells. Therefore, an advanced cure of pathological shifts of AP
requires a creation of medical technologies based on the concept of individual
physiological norm [9].
CONCLUSIONS
The CVS is only a part of EMS that counteracts against lack of ATP in cells.
EMS also includes regulators of lung ventilation, of erythropoiesis, of blood
glucose, and mechanisms regulating the biogenesis of mitochondria. The AP’s
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responsibility concerns only transporting of chemical ingredients to and from cells.
The level of AP is reciprocally associated with the activity of remained functional
blocks of EMS thus their low activity can be compensated via increasing of AP.
A transitory increase of AP supposes one of following scenarios: a) EMS’s
non-hemodynamic reactions are delayed; b) the lack of ATP disappeared due to
spontaneously decreased rate of ATP-consumption. A steady growth of AP
indicates that assistant blocks of EMS cannot provide the adequate power.
A hypotensive cure of AH is advisable only under real risk of a haemorrhage.
In versus cases, the organism is searching for providing of cell energy balance
using non-cardiovascular mechanisms.
A healthy person can have AP essentially different of so-called normal AP.
Under blocking of mechanisms that increase AP, the counteracting mechanisms
use alternative ways for fighting the energy lack. In particular, persons having
more erythrocytes and/or more effective mitochondria do have lower values of AP.
It is necessary to develop medical technologies capable to provide both a
differential diagnostics of main forms of AH and their elimination on initial stages
of development.
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