Sample Chapter TextBook of Human Physiology for Dental Students, 2e by Khurana To Order Call Sms at...

INTRODUCTION

Cardiovascular control makes circulatory adjustments which are essential to cope up with the timely needs of each and every organ of the body, and is thus of fundamental importance for survival.

NEED FOR CARDIOVASCULAR CONTROL

Functions served by cardiovascular control are:

� To increase the blood supply to active tissues, e.g. during exercise to skeletal and cardiac muscles.

� Redistribution of blood to increase or decrease the heat loss from the body as per requirements.

� Circulatory adjustments during routine cardiovascular stresses like change in posture, hours of excitement, fear, anxiety, meals and sleep, etc.

� Maintenance of adequate flow to vital organs, such as brain, heart and kidney, all the times including emergen-cies such as shock and haemorrhage, even at the expense of the circulation to the rest of the body, as the vital

organs may develop irreversible changes in no time. For example, the brain is irreversibly damaged within 3 min of ischaemia, while skin, skeletal muscle and gastroin-testinal tract can tolerate reduction of blood for a longer duration.

CIRCULATORY ADJUSTMENTS

Circulatory adjustments which ensure that all of the organs receive sufficient blood flow are: (1) control of blood vol-ume and (2) control of arterial pressure. These circulatory adjustments are made by the cardiovascular control mecha-nisms primarily by regulating following parameters.

A. Regulation of cardiac performance, i.e. alterations in the activities of heart which include the following.1. Chronotropic action, i.e. effect on heart rate which

may be in the form of: � Increased heart rate (tachycardia) or positive

chronotropic effect. � Decreased heart rate (bradycardia) or negative

chronotropic effect.

CHAPTER

4.5Cardiovascular Regulation

INTRODUCTION � Need for cardiovascular control � Circulatory adjustments � Cardiovascular control mechanisms

NEURAL CONTROL MECHANISMS � Medullary cardiovascular control centres � Autonomic nerve supply to heart and blood vessels � Afferent impulses to medullary cardiovascular control centres � Afferent impulses from higher centres controlling vasomotor centre and cardiac vagal centre

� Afferent impulses from respiratory centres � Cardiovascular reflex mechanisms affecting medullary control centres � Direct effects on vasomotor area

HUMORAL CONTROL MECHANISMS � Circulating vasodilators � Circulating vasoconstrictors � Ions and other chemical factors

LOCAL CONTROL MECHANISMS

Khurana_Ch4.5.indd 177Khurana_Ch4.5.indd 177 9/10/2012 5:22:38 PM9/10/2012 5:22:38 PM

Section 4 ➯ Cardiovascular System178

4SECTION

2. Inotropic action, i.e. effect on force of contraction which may be in the form of: � Increase in the force of contraction (positive ino-

tropic effect) or � Decrease in the force of contraction (negative ino-

tropic effect).

B. Regulation of performance of blood vessels, which primarily includes the following.1. Alterations in diameter of arterioles, which change

the peripheral resistance and also the hydrostatic pressure in the capillaries.

2. Alterations in diameter of veins, which change the venous pressure and thus the venous return and the cardiac output.

CARDIOVASCULAR CONTROL MECHANISMS

The cardiovascular control mechanisms which play their role in making circulatory adjustments during the routine and emergency cardiovascular stresses can be grouped as:

� Neural control mechanism, � Humoral control mechanism and � Local control mechanisms.

NEURAL CONTROL MECHANISMS

Neural regulation of circulation is of fundamental impor-tance since it responds within seconds. The nervous regula-tion mainly controls systemic functions of circulatory system (whenever required) such as:

� Redistribution of blood flow to different parts of the body.

� Increasing pumping activity of heart. � Rapid control of arterial pressure.

Components of neural control mechanism

The neural cardiovascular regulating mechanism consists of the following.

A. Medullary cardiovascular control centres. These are the prime centres concerned with neural control of circulation. These include:

� Medullary sympathetic centre [vasomotor centre (VMC)]. � Medullary parasympathetic centre (nucleus ambiguus). � Medullary relay centre for cardiorespiratory and affer-

ents [nucleus of tractus solitarius (NTS)].

B. Autonomic nervous system supplying the heart and blood vessels. The regulation of circulation by medullary control centres is exerted almost entirely through the autonomic

nervous system (ANS). The sympathetic component of ANS is most important for controlling circulation and the parasympathetic component mainly contributes to the reg-ulation of heart functions.

C. Afferent impulses to medullary centres. The VMC is influenced by afferent impulses from the higher centres and a large number of other areas.

D. Role of skeletal nerves and muscles in controlling blood pressure.

MEDULLARY CARDIOVASCULAR CONTROL CENTRES

1. VASOMOTOR CENTRE

Though popularly known as VMC, more appropriately it should be called as medullary sympathetic centre. It is the primary cardiovascular regulatory centre located in the medulla oblongata of brainstem. It consists of groups of neurons situated bilaterally in the reticular substance of medulla at the floor of fourth ventricle. The medullary car-diovascular centre is constituted by following different areas (Fig. 4.5-1).

Pressor area

Pressor area is located in the rostral ventrolateral medulla (RVLM). It contains glutaminergic neurons which exert excitatory effect on the thoracolumbar spinal sympathetic neurons.

Continuous sympathetic vasoconstrictor tone. Nor mally, the neurons forming pressor area of the VMC show inher-ent tonic activity, i.e. they discharge rhythmically (at a rate of about 1 impulse per second) in a tonic fashion to excite sympathetic preganglionic neurons present in the interme-diolateral grey column of the spinal cord. In this way, the continuous signals are passed to the sympathetic vasocon-strictor nerves fibres over the entire body. Sympathetic vaso-constrictor tone.

Pressor area(RVLM)

Depressor area(CVLM)

Fig. 4.5-1 Medullary cardiovascular control centres.


Chapter 4.5 ➯ Cardiovascular Regulation 179

4SECTION

Stimulation of pressor area produces:

� Arteriolar constriction, which increases the systemic blood pressure.

� Venoconstriction, which decreases blood stored in the venous reservoir and increases venous return.

� Increase in heart rate or positive chronotropic effect. � Increase in force of contraction or positive inotropic effect.

Depressor area

Depressor area is situated bilaterally in the caudal ventro-lateral medulla (CVLM). Stimulation of neurons forming depressor area produces decrease in the sympathetic activ-ity due to inhibition of the tonically discharging impulses of the pressor area causing:

� Arteriolar dilation, which decreases systemic blood pressure.

� Venodilatation, which increases storage of blood in the venous reservoir and decreases venous return and cardiac output.

� Decrease in heart rate or negative chronotropic effect. � Decrease in force contraction or negative inotropic effect.

2. MEDULLARY PARASYMPATHETIC CENTRE

Medullary parasympathetic centre or cardiac vagal centre (earlier also called cardioinhibitory centre) is now called by its specific name, i.e. the nucleus ambiguus. The neurons located in this centre are not tonically active. Nucleus ambiguus receives afferents via NTS and in turn sends inhibitory pathway in the form of vagal fibres to: heart to decrease the heart rate and force of cardiac contraction.

3. MEDULLARY RELAY STATION FOR CARDIORESPIRATORY AFFERENTS

NTS of the vagus nerve forms the so-called medullary relay station for the cardiorespiratory afferents. It receives affer-ents from most of the baroreceptors and chemoreceptors. Cells of the NTS, in turn, relay the information to VMC and cardiac vagal centre (nucleus ambiguus) that control sym-pathetic and parasympathetic outputs, respectively.

AUTONOMIC NERVE SUPPLY TO HEART AND BLOOD VESSELS

AUTONOMIC NERVE SUPPLY TO HEART

Sympathetic supply

Spinal sympathetic centre is formed by the neurons located in the intermediolateral horns of the spinal cord extending from T1 to L2 spinal segments.

� Preganglionic sympathetic fibres (small, myelinated) supplying the heart arise from the neurons lying in the

intermediolateral horns of the T1–T5 spinal segments and pass into the sympathetic trunk to superior, middle and inferior cervical ganglia, and upper thoracic ganglia where they synapse (Fig. 4.5-2).

� Postganglionic fibres (long, unmyelinated) leave the gan-glia and pass via superior, middle and inferior cardiac sympathetic nerves, and supply to the nodal tissues [sinoatrial (SA) node and atrioventricular (AV) node] and the cardiac muscles of atria and ventricles (Fig. 4.5-2). It is important to note that:– Sympathetics from the right side are primarily dis-

tributed to the SA node.– Sympathetics from the left side are primarily distrib-

uted to the AV node.

Stimulation of cardiac sympathetic nerves causes:

� Increased heart rate (positive chronotropic effect), � Increase in the conduction of impulse through heart

(positive dromotropic action), � Increase in the excitability of myocardium (positive

bathmotropic effect) and � Increase in the force of contraction of myocardium (posi-

tive inotropic effect).

Parasympathetic supply

Parasympathetic fibres to the heart are carried through two vagii (Fig. 4.5-3).

Preganglionic fibres (long, myelinated) arise from the nucleus ambiguus located in the medulla and travel along the vagii to reach the heart through their cardiac branches to synapse in the ganglia located within the superficial and deep cardiac plexuses and also in the walls of atria.

Postganglionic fibres (small, unmyelinated) are distrib-uted to the atria, SA node, AV node and AV bundle. It is important to note that:

� The right vagus is distributed mainly to SA node, � The left vagus is distributed mainly to AV node, � No vagal motor fibres are distributed to the ventricles and � Parasympathetic fibres to the heart are endocardiac.

Stimulation of parasympathetic fibres to heart causes:

� Decrease in heart rate (negative chronotropic effect). � Decrease in conduction of impulse through the conduc-

tion tissue (negative dromotropic effect). � Decrease in the excitability of atria only (negative bath-

motropic effect). � Decrease in the force of contraction of atria only (nega-

tive inotropic effect). There is no effect on the force of contraction of ventricles.

Vagal tone. There is a good deal of tonic vagal discharge, called the vagal tone, in humans and other large animals.



4SECTION

Nucleus tractussolitarius (NTS)

Dorsal motor nucleus

Nucleus ambiguus

Vagus nerve

Preganglionicparasympathetic fibres

Postganglionicparasympathetic fibresHeart

Fig. 4.5-3 Parasympathetic innervation of the heart.

Therefore, when vagii are cut in the experimental animals, the heart rate rises. Similarly, in adult humans, the resting heart rate which is about 72 beats/min rises to 150–180 beats/min after the administration of vagolytic drugs, such as atropine, because of the unopposed sympathetic tone. When both adrenergic and cholinergic systems are blocked in humans, the heart rate is approximately 100 beats/min. Since the resting heart rate is about 72/min, it confirms that at rest the vagal tone is greater than the sympathetic tone.

AUTONOMIC NERVE SUPPLY TO BLOOD VESSELS

The autonomic efferents supplying the blood vessels pro-duce two types of effects.

Vasoconstriction effect

Vasoconstriction effect is produced by the sympathetic fibres supplying the blood vessels which originate from the intermediolateral horns in T1–L2 spinal segments.

Vasoconstrictor fibres have norepinephrine and some-times neuropeptide Y as neurotransmitter, and are called noradrenergic fibres.

Sympathetic vasoconstrictor fibres show tonic (i.e. con-tinuous) discharge at the rate of about 1 impulse/s. There-fore, when the sympathetic nerves are cut (sympathectomy) there occurs:

� Vasodilation – which leads decreased peripheral resis-tance → decreased diastolic blood pressure.

� Venodilatation – increased venous capacity → decreased venous return → decreased end-diastolic volume → decreased stroke volume → decreased cardiac output → decreased systolic blood pressure.

Stimulation of sympathetic fibres produces: � Constriction of arterioles – increased peripheral resis-

tance → increased diastolic blood pressure. � Venoconstriction – decreased venous capacity →

increased venous return → increased end-diastolic vol-ume → increased stroke volume → increased cardiac output → increased systolic blood pressure.

Medulla

Nucleus ambiguus

Cardiac nerves(Postganglionic

sympathetic fibres)

Blood vessels

Late

ral s

ympa

thet

ic c

hain

Preganglionicsympathetic

fibres

Spinal cord

Nucleus tractus solitarius

NTS

Pressor areaDepressor area

Adrenal medulla

Interomediolateralspinal sympathetic

neurons

Splanchnicnerves

AV node

SA node

Superior cervical ganglion

Middle cervical ganglion

Inferior cervical ganglion

Fig. 4.5-2 Sympathetic innervation to heart and blood vessels.



4SECTION

Both these mechanisms are responsible for the regional redistribution of blood and at the time of need the blood is diverted from the skin, skeletal muscles and splanchnic area to the heart and brain.

Vasodilation effect

Neural vasodilation effect on the blood vessels is produced by following mechanisms.

1. Decrease in discharge of noradrenergic vasoconstrictor nerves.

2. Sympathetic cholinergic vasodilator nerves. Some of the organs of the body, such as skeletal muscles, heart, lungs, liver, kidney and uterus in addition to adrenergic vasoconstrictor sympathetic fibres also receive innervation by cholinergic vasodilator sympathetic fibres having acetyl-choline and vasoinhibitory peptide (VIP) as neurotransmit-ter. These fibres originate from the cerebral cortex, relay in the hypothalamus and midbrain, and pass through the medulla (without relay in the VMC) to the sympathetic neurons located in the intermediolateral grey column of the spinal cord (Fig. 4.5-4). These fibres are not tonically active and get activated only in biological stresses, for example during exercise, child birth, etc. and help in increasing the blood flow.

3. Parasympathetic vasodilator nerves

� Blood vessels, in general, do not have parasympathetic innervation with following exceptions:– Sacral outflow parasympathetic fibres represented by

nervi erigentes, which supplies sexual erectile tissue and is responsible for vasodilation in external genita-lia during sexual excitement.

– Cranial outflow of parasympathetic fibres along chorda tympani branch of facial nerve to salivary glands.

– The postganglionic cholinergic neurons on the blood vessels contain acetylcholine, VIP and PHM-27 as neurotransmitters.

It is important to note that parasympathetic vasodilator fibres play little role in the control of general circulation. Activation of such nerves only contributes to pleasure and fulfilling important biological functions.

4. Vasodilation by axon reflex. Conduction of normal sen-sory afferent impulses from the skin to spinal cord is called orthodromic conduction. However, in certain situations, for example, when a firm stroke is applied across the skin the afferent impulses in the sensory nerves from the skin are relayed antidromically down branches of the sensory nerves that innervate blood vessels (Fig. 4.5-5). The anti-dromic conduction of impulses causes release of substance P from the nerve endings, which produces vasodilation and increases capillary permeability. This local neural mecha-nism (which does not involve the CNS) is called axon reflex. It is responsible for the local vasodilation and does not con-tribute in systemic control of circulation.

AFFERENT IMPULSES TO MEDULLARY CARDIOVASCULAR CONTROL CENTRES

The medullary control centres are influenced by afferent control impulses from the higher centres and a large num-ber of other areas (Fig. 4.5-6). These include: � Afferent impulses from higher centres controlling

VMC.

LEFT RIGHT

Medulla oblongata(Pressor area, IML cells)Preganglionic sympathetic fibres

Postganglionicsympathetic fibres

Noradrenaline

Blood vessels

Adrenal medullaAdrenaline

Preganglionicsympathetic fibres to adrenal medulla

ACh

ACh

Sympatheticvasodilator fibres

to skeletal muscleblood vessels

Cerebral cortex

Hypothalamus

ACh

Fig. 4.5-4 Pathway of sympathetic vasodilator fibres (on left side) and sympathetic vasoconstrictor system (on right side).

Dorsal root ganglia

Orthodromicconduction

Spinal cord

Skin nerveendings

Antidromic conduction

Arteriolar endings

Fig. 4.5-5 Pathway of axon reflex.



4SECTION

Spinal cord

Lateralsympathetic chains

Pressorarea

Depressorarea

Vasomotorcentre

Hypothalamus

Cerebralcortex

Respiratorycentre

Emotions

PainC

hem

orec

epto

rs

Bar

orec

epto

rs

Sympatheticfibres

CIC

Bloodvessels

VasoconstrictionVenoconstriction

Heart rate

Stroke volumeHeart

Fig. 4.5-6 Scheme to show afferent impulses affecting medullary cardiovascular control centres.

� Afferent impulses from respiratory centres. � Cardiovascular reflex mechanisms operating through

medullary control centres.– Baroreceptor reflex– Chemoreceptor reflexes

� Direct effects on vasomotor area.– Central nervous system (CNS) ischaemic response– Cushing reflex

� Afferents from nociceptive stimuli.

AFFERENT IMPULSES FROM HIGHER CENTRES CONTROLLING VASOMOTOR CENTRE AND CARDIAC VAGAL CENTRE

CEREBRAL CORTEX

There are descending tracts to the vasomotor area from the cerebral cortex (particularly the limbic cortex) that relay in

the hypothalamus. Some examples of the influence of lim-bic system on the VMC are:

� Tachycardia and hypertension produced by emotions. � Bradycardia and fainting occurring during sudden

emotional shock. � Fight or flight response is a complex set of response

which increases cardiac output and raises blood pres-sure in anticipation of flight or physical defence.

HYPOTHALAMUS

The hypothalamus serves to integrate many somatic and autonomic responses. Examples are:

� Temperature regulation. The effect of temperature changes on the hypothalamic centres is relayed to the medulla, which causes the vessels of skin to constrict (heat conservation) or to dilate (heat dissipation).



4SECTION

� Emotional stresses influence heart rate and blood pres-sure by impulses relayed from the hypothalamus to stimulate or inhibit the medullary centres.

RETICULAR FORMATION

Reticular formation of pons, mesencephalon and dienceph-alon also influences the vasomotor area, for example:

� Pain usually causes rise in the blood pressure via afferent impulses in the reticular formation converging on the vasomotor area. However, prolonged severe pain may cause vasodilation and fainting.

AFFERENT IMPULSES FROM RESPIRATORY CENTRES

Impulses arising from the respiratory centres affect the heart rate by changing the vagal tone, and the alterations produced are known as sinus arrhythmia which occurs dur-ing forced breathing.

� During inspiration, the impulses arising from the respira-tory centres during inspiration inhibit the cardiac vagal centre causing reduced vagal tone and sinus tachycardia.

� During expiration, the respiratory centres stop sending inhibitory impulses to the cardiac vagal centre causing increased vagal tone and sinus bradycardia.

CARDIOVASCULAR REFLEX MECHANISMS AFFECTING MEDULLARY CONTROL CENTRES

Cardiovascular reflex mechanisms are multiple subcon-scious special nervous control mechanisms that operate through medullary control centres all the time to maintain the arterial pressure within normal range. These include:

� Baroreceptor reflex mechanisms and � Chemoreceptor reflex mechanism.

BARORECEPTOR REFLEX MECHANISMS

Baroreceptors, also known as mechanoreceptors or pres-sure receptors, are the stretch receptors located in the walls of heart and large blood vessels. These are spray-type nerve endings, i.e. they are extensively branched, knobby, coiled and intertwined ends of myelinated nerve fibres. These are stimulated by distension of the structures in which they are located and so they discharge at an increased rate when the pressure in these structures rises. The increased baro-receptor discharge leads to inhibition of tonic discharge of vasoconstrictor nerves and excitation of vagal innervation of heart, and thereby produces vasodilation, venodilation, bradycardia, decrease in cardiac output and decrease in blood pressure.

With this definition of the baroreceptor reflex mecha-nism the baroreceptors will be discussed in detail as under following headings.

CLASSIFICATION AND LOCATION OF BARORECEPTORS

Functional classification

Functionally baroreceptors can be grouped as follows.

1. High-pressure baroreceptors, which monitor the arterial circulation. These include the baroreceptors located at: � Carotid sinus, � Aortic arch, � Wall of left ventricle, � Root of right subclavian artery and � Junction of the thyroid artery with common carotid

artery.2. Low-pressure baroreceptors are located in the low-

pressure area of circulation and are collectively referred to as cardiopulmonary receptors. These include: � Atrial receptors scattered in the wall of right and left

atrium. � Baroreceptors located in the right atrium at the

entrance of the superior and inferior vena cavae and in the left atrium at the entrance of pulmonary veins.

� Pulmonary receptors located in the wall of pulmo-nary trunk and its divisions into the right and left pulmonary artery.

CAROTID AND AORTIC ARCH BARORECEPTORS

Location of carotid and aortic arch baroreceptors

Carotid baroreceptors are located in the carotid sinus, which is a small dilatation of the internal carotid artery just

Carotid body

Aortic body

External carotid artery

Carotid sinus baroreceptors

Common corotid artery

Aortic arch baroreceptors

Fig. 4.5-7 Location of baroreceptors (carotid sinus and aortic

arch) and chemoreceptors (carotid bodies and aortic bodies).



4SECTION

above the bifurcation of the common carotid artery into external and internal carotid branches (Fig. 4.5-7).

Aortic arch baroreceptors are located in the wall of arch of aorta (Fig. 4.5-7).

Other systemic arterial baroreceptors (similar to carotid and aortic baroreceptors) are also found at the root of right subclavian artery and junction of thyroid artery, and in the common carotid artery.

Innervation of baroreceptors (Fig. 4.5-8)

Carotid sinus baroreceptors are innervated by the carotid sinus nerve (Hering’s nerve), which is a branch of glosso-pharyngeal nerve.

All other baroreceptors are supplied by the vagus nerve.

Afferent fibres from the baroreceptors pass via the glos-sopharyngeal and vagus nerves to the medulla. Most of them end in the NTS, where they secrete an excitatory transmit-ter, presumably, glutamate.

Buffer nerves. The carotid sinus nerve and vagal fibres from the carotid sinus and aortic arch baroreceptors, respectively, are commonly called buffer nerves because these are involved in buffering the blood pressure, i.e. pre-venting sudden rise and fall in the blood pressure.

Projections from NTS (excitatory glutaminergic projec-tions) terminate on to the:

� Depressor area of VMC, where they stimulate GABA (gamma-aminobutyric acid)-secreting inhibitory neu-rons which decrease sympathetic activity.

� Cardiac vagal centre (nucleus ambiguus), after receiving the impulses from NTS, sends inhibitory pathway along the vagus nerve to:– Heart (through cardiac branches of the vagus nerve

to decrease heart rate and force of contraction).

Response of carotid and aortic baroreceptors to pressure

Response from carotid baroreceptors have been studied in detail. Salient features of these receptor’s responses to pressure are given below.

Baroreceptor response. At normal blood pressure levels the fibres of the buffer nerves discharge at a low rate which increases when the pressure in the carotid sinus and aortic arch rises, and declines when the pressure falls (Figs 4.5-9 and 4.5-10).

The effect of different arterial pressure levels on the dis-charge rate in carotid sinus nerve shown in Fig. 4.5-10 depicts that:

� The minimum pressure of about 60 mm Hg at which carotid baroreceptors are stimulated is called threshold of baroreceptor reflex.

� Above threshold level, the baroreceptors respond pro-gressively more rapidly till the discharge rate reaches a plateau, at 150–160 mm Hg, i.e. there is no further increase in response. Thus, the carotid baroreceptors

Afferent NTS

NAm

Depressor area

Pressor area

IX N X N

Sinus N

Carotidsinus

Aortic arch

Aortic N

Vagus nerveactivity increases

Efferent

Sympatheticdischargedecreases

GABA

Fig. 4.5-8 Neural pathway of baroreceptor reflex.

0 0.5 1.0 1.5Time (s)

2.0

50

80

100

200

120

Aor

ticpr

essu

re(p

hasi

c)

Mea

n ar

teria

l pre

ssur

e (m

mH

g)

Fig. 4.5-9. Discharges (vertical lines) in a single afferent nerve

fibre from carotid sinus at various levels of mean arterial

pressure, plotted against changes in aortic pressure with time.



4SECTION

exhibit a great sensitivity as they respond to pressure that varies from approximately 50–160 mm Hg.

� In the normal operating rate at 95–100 mm Hg, even a slight change in pressure causes a strong change in the baroreceptor reflex signals to readjust the arterial pres-sure back towards the normal.

� When pressure decreases below normal levels, the baro-receptor discharge decreases and reflexly brings the pressure to normal. Conversely, when pressure increases above normal, the baroreceptor discharge also increases and reflexly brings the pressure to normal.

The carotid baroreceptors respond both to the mean pressure and the pulse pressure. Thus, the baroreceptor discharge would increase:

� When the mean pressure rises and the pulse pressure remains unchanged or

� When the pulse pressure rises and the mean pressure remains unchanged.

Carotid baroreceptors respond much more to a rapidly changing pressure than to a stationary pressure.

Pressure–buffer system of baroreceptors. From the above description it is clear that baroreceptor system opposes both increase as well as decrease in the arterial pressure. Therefore, it is called a pressure–buffer system and the nerves from the baroreceptors are called buffer nerves.

Baroreceptors resetting. Baroreceptors possess a prop-erty to reset themselves in 1–2 days to whatever pressure they are exposed. Therefore, in chronic hypertension the baroreceptor reflex mechanism resets to maintain an ele-vated rather than a normal arterial pressure. Because of this property the baroreceptor system has no role to play for long-term regulation of the mean arterial pressure. Thus, the baroreceptor reflex mechanism plays an important role only in preventing the extreme variations in blood pressure which occur for a short term.

CARDIAC BARORECEPTORS

Cardiac baroreceptors are located in the walls of heart sub-endocardially. All cardiac receptors are innervated by the vagus nerve. These include the following.

Atrial stretch receptors

Atrial stretch receptors present in the walls of atria are also called low-pressure receptors.

Atrial stretch receptors have been studied in detail by Prof. AS Paintal (an Indian scientist) in 1953.

Role of atrial stretch receptorsThe atrial stretch receptors have been associated with following roles in the cardiovascular control.

1. As low-pressure receptors. The atrial stretch receptors along with pulmonary receptors play an important role to minimize arterial pressure changes in response to change in blood volume. Low-pressure receptors cannot detect the systemic arterial pressure, they do provide information about the circulating blood volume, i.e. greater the venous return, greater will be the discharge from the receptor fibres.

2. Atrial reflex control of heart rate (Bainbridge reflex). Bainbridge noted that sudden rise in the atrial pressure after rapid infusion of saline or blood in anaesthetised ani-mals produced tachycardia, if the initial heart rate was low. This effect is known as Bainbridge reflex. Atrial stretch receptors may be responsible for this reflex. The afferent signals from these receptors pass through the vagus nerves to the medulla of brain. The efferent signals are transmitted back through both the vagal and the sympathetic nerves to increase the heart rate and force of contraction. Thus, this reflex helps to prevent damming of blood in the veins, atria and pulmonary circulation.

3. Atrial reflex control of blood volume (volume reflex). When there is volume overload the atrial stretch receptors help to return the blood volume back towards normal by following mechanisms, which collectively are called volume reflex:(i) Stretch of the atria causes very significant reflex dilata-

tion of the afferent arterioles in the kidney leading to rise in glomerular capillary pressure with resultant increase in filtration of fluid into the kidney tubules.

(ii) Stretch of the atria also transmits signals to the hypo-thalamus to decrease the secretion of antidiuretic hor-mone (ADH), which diminishes the reabsorption of water from tubules.

(iii) Stretch of the atria also causes release of a chemical called atrial natriuretic peptide (ANP), which causes powerful diuresis and thus brings blood volume back to normal.

Dis

char

ge r

ate

of s

inus

ner

ve(N

umbe

r of

impu

lses

/s)

0 60 120 180 240

Arterial pressure (mm Hg)

Fig. 4.5-10 Response of carotid baroreceptors at different

levels of arterial pressure.



4SECTION

The above described mechanisms (i–iii), which collec-tively constitute volume reflex, act as a volume controller and thus indirectly act as a pressure controller as well. Because excess volume increases the cardiac output and thus the arterial pressure as well.

Ventricular receptors

The ventricular baroreceptors are scattered throughout the left ventricle and interventricular septum. They discharge irregularly and no physiological significance can be attached to these receptors.

Bezold–Jarisch reflex or coronary chemoreflex refers to the reflex apnoea followed by rapid breathing, hypotension and bradycardia, which occur following injection of certain drugs like serotonin, veratridine or nicotine into the coro-nary arteries supplying the left ventricle (injection into the right coronary artery is ineffective) in experimental ani-mals. This reflex is probably produced by the chemical stimulation of the left ventricular stretch receptors.

� Physiological significance of this reflex is uncertain, but it has been speculated that the persistent hypotension in some patients of acute myocardial infarction may be due to stimulation of the ventricular receptors by sub-stances released from the necrotic cardiac tissue.

PULMONARY BARORECEPTORS

Pulmonary baroreceptors are located in the walls of pulmo-nary trunk and its divisions, the right and left pulmonary artery. The pulmonary receptors along with the atrial receptors constitute the so-called low-pressure receptors or cardiopulmonary receptors, and play an important role to minimize arterial pressure changes in response to change in blood volume as discussed above (see page 183).

ROLE OF CHEMORECEPTOR REFLEXES IN CARDIOVASCULAR CONTROL

Chemoreceptors are chemosensitive cells that respond to following changes in blood:

� Oxygen lack (decreased PO2), � Carbon dioxide excess (increased PCO2) and � Hydrogen ion excess (decreased pH).

Location of chemoreceptor. The chemoreceptors are pres-ent in (Fig. 4.5-7):

1. Carotid bodies. These are 1–2 mm in size and are located in the bifurcation of each common carotid artery. These are innervated by carotid sinus nerve, which is a branch of glossopharyngeal nerve.

2. Aortic bodies are one to three in number, located adja-cent to arch of aorta. These are innervated by aortic nerve (branch of vagus nerve).

Functions of chemoreceptors

1. Respiratory control. Chemoreceptors are primarily con-cerned with the regulation of pulmonary ventilation and are discussed in much more detail in Chapter 5.6, page 245.

2. Cardiovascular control. The chemoreceptors exert their role in cardiovascular regulation in following conditions: � In hypoxia, there occurs increased chemoreceptor

discharge, which not only produces hyperventilation but also excites the VMC leading to peripheral vaso-constriction and increase in the arterial blood pres-sure. Thus, unlike the inhibitory action of arterial baroreceptors, the chemoreceptors have an excit-atory effect on the VMC.

� In hypotension due to severe haemorrhage, the increased chemoreceptor discharge may help to raise the arterial blood pressure.

Note. It is important to note that the chemoreceptors are not stimulated strongly until the arterial pressure falls below 60 mm Hg. Therefore, it is at lower pressures that this reflex becomes important and helps to prevent still fur-ther fall in pressure.

DIRECT EFFECTS ON VASOMOTOR AREA

The VMC is directly affected by locally produced hypoxia and hypercapnia. Examples of direct effects are CNS isch-aemic response and Cushing reflex.

1. Central nervous system ischaemic response

� When blood pressure falls below 60 mm Hg, the blood flow to the vasomotor area in the brainstem is decreased enough to cause CNS ischaemia.

� As a result of CNS ischaemia, the CO2/lactic acid are accumulated locally near the VMC and excite the neu-rons of VMC strongly.

� Excitation of VMC causes strong sympathetic stimula-tion leading to vasoconstriction. There occurs immedi-ate increase in the blood pressure. This most powerful response that activates sympathetic vasoconstrictor system strongly is called CNS ischaemic response. This acts as an emergency arterial pressure control system.

2. Cushing reflex

When intracranial pressure is increased and becomes equal to the arterial pressure, it compresses the arteries in the brain, and blood supply to the vasomotor area is compro-mised. The hypoxia and hypercapnia produced locally increase the discharge from VMC. The resultant rise in the systemic pressure tends to restore the blood supply to medulla. This effect is called Cushing reflex. The resultant increase in blood pressure also causes reflex bradycardia



4SECTION

via baroreceptor response. Thus, bradycardia is an impor-tant feature of raised intracranial pressure.

AFFERENTS FROM NOCICEPTIVE STIMULI

Afferents carrying pain sensations also affect VMC and evoke either pressor or depressor reflex effect as:

Pressor effect in the form of an increase in the blood pres-sure and tachycardia is caused due to the sympathetic activ-ity by somatic pain afferents, i.e. unmyelinated C-fibres which stimulate the pressor area of VMC.

Depressor effect in the form of hypotension and bradycar-dia is produced by visceral pain afferents, i.e. thin myelin-ated fibres which synapse with depressor area of VMC and cause inhibition of sympathetic activity.

HUMORAL CONTROL MECHANISMS

Humoral regulation of circulation refers to the regulation by substances secreted into or absorbed into body fluids, e.g. hormones, ions, etc. Most important humoral factors affecting circulation are:

� Circulating vasodilators, � Circulating vasoconstrictors, and � Ions and other chemical factors.

CIRCULATING VASODILATORS

The circulating vasodilators include the following.

KININS

Kinins are peptides which cause vasodilation. Two forms of kinins with similar action found are:

� Bradykinin is nonapeptide found in the plasma and � Lysyl-bradykinin or kallidin is a decapeptide found in

body tissues.

Functions of kinins

� They cause vasodilation by relaxing vascular smooth muscle (VSM) via nitric oxide (NO) and increase capil-lary permeability.

� Kinins play role in regulating blood flow especially to skin, salivary glands and GIT glands. Therefore, they are formed during active secretion in sweat glands, salivary glands and in exocrine portion of pancreas.

� By regulating blood flow to skin the kinins probably play a role in thermoregulatory vascular adjustments.

ATRIAL NATRIURETIC PEPTIDE

See page 188.

CIRCULATING VASOCONSTRICTORS

The circulating vasoconstrictors include catecholamines, angiotensin II and vasopressin.

CATECHOLAMINES

Catecholamines are released on the sympathetic stimula-tion and include the following.

Epinephrine. It stimulates both α and β adrenergic receptors:

� Stimulation of α-receptors results in vasoconstriction in skin and splanchnic areas.

� Stimulation of β-receptors results in dilation of the ves-sels in the skeletal muscles, liver and coronary arteries.

� The β-receptor-induced vasodilation is more dominant than α-receptors-induced vasoconstriction. So, the net effect is slight lowering of peripheral resistance produc-ing slight fall in diastolic blood pressure.

Norepinephrine. It has a generalized vasoconstrictor action as it has much greater effect on α- than on β-receptors. Therefore, it increases peripheral resistance and raises the diastolic blood pressure.

RENIN–ANGIOTENSIN SYSTEM

The renin–angiotensin system has important roles in the regulation of blood pressure and extracellular fluid volume.

Renin secretion and angiotensin formation

� Renin, a protease enzyme is secreted by juxtaglomerular cells of the kidney into the blood. Its secretion is stimu-lated by a decrease in the blood pressure.

� Renin catalyzes the conversion of angiotensinogen (α2-globulin substrate present in the plasma) to angio-tensin I.

� Angiotensin I is converted into angiotensin II by the action of angiotensin converting enzyme (ACE) present in the endothelium of blood vessels throughout the body, especially in the lungs and kidneys.

Renin

ACEAngiotensinogen Angiotensin I

Angiotensin I Angiotensin II

⎯⎯⎯→

⎯⎯⎯→

Effects of angiotensin II

Angiotensin II has three principal effects by which it can elevate the arterial pressure.

1. Vasoconstriction. Angiotensin II is the most potent pres-sor substance being 4–8 times more potent than norepi-nephrine. This effect of angiotensin II is important in the



4SECTION

intermediate blood pressure control during circumstances, such as acute haemorrhage.

2. Decrease in salt and water excretion by kidney. Angiotensin II causes salt and water retention by the kid-ney. This action slowly increases extracellular fluid volume, which increases arterial pressure over a period of hours and days. Thus, this effect of angiotensin II plays an important role in the long-term control of arterial pressure.

3. Stimulation of thirst. Angiotensin II is a powerful stimula-tor of thirst. It leads to consumption of large volumes of water, leading to a rise in blood volume. This mechanism also plays some role in long-term control of blood pressure.

VASOPRESSIN

Vasopressin or ADH is secreted in minute quantities and therefore mainly affects water reabsorption in renal tubules. However, after a severe haemorrhage its concentration rises to a high level and then it has vasoconstrictor effect.

IONS AND OTHER CHEMICAL FACTORS

The increased concentration of many different ions and chemical factors can also alter local blood flow by causing vasodilation or vasoconstriction.

� Calcium ions cause vasoconstriction. � Potassium ions cause vasodilation. � Hydrogen ions (decreased pH) cause vasodilation. � Carbon dioxide causes vasodilation in most tissues and

marked vasodilation in the brain. � Glucose or other vasoactive substances, when increased

in quantities, raise the osmolarity of blood and cause vasodilation.

LOCAL CONTROL MECHANISMS

Local cardiovascular control mechanisms are primarily con-cerned with the control of blood flow to the tissues locally.

The mechanisms that are present in most tissues of the body are:

1. Autoregulation, i.e. control of flow during changes in the arterial pressure,

2. Role of local vasodilator metabolites and factors,3. Role of local vasoconstrictors, and4. Role of substances secreted by the endothelial cells.

1. Autoregulation (control of flow during changes in arterial pressure)

Autoregulation is the ability of an organ or tissue to adjust its vascular resistance and maintain a relatively constant

blood flow over a wide range of arterial pressure. For details see page 167.

2. Role of local vasodilator metabolites

The accumulation of local vasodilator metabolites increases local blood flow. The greater the rate of metabolism in the tissue, the greater is the rate of production of tissue metab-olites. These include:

� Decrease in O2 tension and pH, � Increase in pCO2 and osmolality, � Rise in temperature, � Potassium (K+) and lactate ions, � Histamine and � Adenosine.

Local vasodilator metabolites increase blood flow dur-ing following conditions.

Active hyperaemia refers to the vasodilation which occurs when the tissue metabolic rate increases. The dilation of local blood vessels helps the tissues to receive the additional nutrients required to sustain its new level.

Metabolic theory of autoregulation states that any vaso-dilator metabolites which accumulate in the tissues during active metabolism will produce autoregulation. When blood flow decreases, they accumulate and the vessels dilate; when blood flow increases, they are washed away.

Reactive hyperaemia is a phenomenon by which the local blood flow to the organ is controlled after a period of ischaemia.

3. Role of localized vasoconstrictors

Serotonin released from platelets in the injured tissue is responsible in part for the vasoconstriction, which occurs in haemostasis.

Decrease in tissue temperature causes vasoconstriction and this local response to cold plays a part in temperature regulation.

4. Role of substances released by endothelium

Vascular endothelial cells make up a large and important organ. These cells secrete many growth factors and vasoac-tive substances, which play an important role in the local control of blood flow. The vasoactive substances include:

� Prostaglandins and thromboxane A2, � Endothelium-derived relaxing factor (EDRF) and � Endothelins.

(i) Prostaglandins and thromboxane A2

� Prostacyclin is prostaglandin produced by the endo-thelial cells from arachidonic acid via cyclooxygenase



4SECTION

pathway. It inhibits platelet aggregation and promotes vasodilation.

� Thromboxane A2 is produced by platelets and also from arachidonic acid. It promotes platelet aggregation and vasoconstriction.

(ii) Endothelium-derived relaxing factorEDRF is the name given to a substance which is released by vascular endothelial cells and produces vasodilation. Later on, it was identified to be nitric oxide (NO) in chemical structure.

Mechanism of vasodilation by NO. The NO that is syn-thesized in the endothelium diffuses to smooth muscle cells, where it activates soluble guanylyl cyclase, producing cyclic GMP, which in turn mediates the relaxation of VSM by decreasing intracellular Ca2+ concentration.

(iii) Endothelins (ET)Endothelins are family of three similar polypeptides: ET-1, ET-2 and ET-3. Endothelin-1 produced by the endothelial cells is the most potent vasoconstrictor agents.


Sample Chapter TextBook of Human Physiology for Dental Students, 2e by Khurana To Order Call Sms at...

Documents

Transcript of Sample Chapter TextBook of Human Physiology for Dental Students, 2e by Khurana To Order Call Sms at...