The cardiovascular system is centrally regulated by autonomic reflexes.
These work with local mechanisms (see Chapter 23) and the renin–angiotension–aldsterone
and antidiuretic hormone systems (see Chapter 29) to minimize
fluctuations in the mean arterial blood pressure (MABP) and volume, and to
maintain adequate cerebral and coronary perfusion. Intrinsic reflexes,
including the baroreceptor, cardiopulmonary and chemoreceptor reflexes,
respond to stimuli originating within the cardiovascular system. Less important
extrinsic reflexes mediate the cardiovascular response to stimuli
originating elsewhere (e.g. pain, temperature changes). Figure 27 illustrates
the responses of the baroreceptor and cardiopulmonary reflexes to reduced blood
pressure and volume, as would occur, for example, during haemorrhage.
Cardiovascular reflexes involve three components:
1 Afferent nerves (‘receptors’) sense a change in
the state of the system, and communicate this to the brain, which
2 Processes this information and implements an
appropriate response, by
3 Altering the activity of efferent nerves
controlling cardiac, vascular and renal function, thereby causing homeostatic
responses that reverse the change in state.
Intrinsic cardiovascular reflexes
The baroreceptor reflex
This reflex acts rapidly to minimize moment-to-moment fluctuations in the
MABP. Baroreceptors are afferent (sensory) nerve endings in the walls of the carotid sinuses (thin-walled
dilatations at the origins of the internal carotid arteries) and the aortic
arch. These mechanoreceptors sense alterations in wall stretch
caused by pressure changes, and respond by modifying the frequency at which
they fire action potentials. Pressure elevations increase impulse frequency;
pressure decreases have the opposite effect.
When MABP decreases, the fall in baroreceptor impulse frequency causes
the brain to reduce the firing of vagal efferents supplying the
sinoatrial node, thus causing tachycardia. Simultaneously, the activity of
sympathetic nerves innervating the heart and most blood vessels is increased,
causing increased cardiac contractility and constriction of arteries and veins.
Stimulation of renal sympathetic nerves increases renin release, and
consequently angiotensin II production and aldosterone secretion (see Chapter
29). The resulting tachycardia, vasoconstriction and fluid retention act
together to raise MABP. Opposite effects occur when arterial blood pressure
rises.
There are two types of baroreceptors. A fibres have large, myelinated
axons and are activated over lower levels of pressure. C fibres have
small, unmyelinated axons and respond over higher levels of pressure. Together,
these provide an input to the brain which is most sensitive to pressure changes
between 80 and 150 mmHg. The brain is able to reset the baroreflex to allow
increases in MABP to occur (e.g. during exercise and the defence reaction).
Ageing, hypertension and atherosclerosis decrease arterial wall compliance,
reducing baroreceptor reflex sensitivity.
The baroreceptors quickly show partial adaptation to new pressure
levels. Therefore alterations in frequency are greatest while pressure is
changing, and tend to moderate when a new steady- state pressure level is established. If
unable to prevent a change in MABP, the reflex will within several hours become
reset to maintain pressure around the new level. This finding, together
with studies by Cowley and coworkers in the 1970s showing that destroying
baroreceptor function increased the variability of MABP but had little effect
on its average value measured over a long time, led to general acceptance of
the idea that baroreceptors have no role in long-term regulation of MABP.
However, recent evidence that baroreceptor resetting is incomplete and that
electrical stimulation of baroreceptors causes reductions in MABP which are
sustained over many days has led some experts to re-evaluate this issue.
Diverse intrinsic cardiovascular reflexes originate in the heart and
lungs. Cutting the vagal afferent fibres mediating these cardiopulmonary
reflexes causes an increased heart rate and vasoconstriction, especially in
muscle, renal and mesenteric vascular beds. Cardiopulmonary reflexes are
therefore thought to exert a net tonic depression of the heart rate and
vascular tone. Receptors for these
reflexes are located mainly in low-pressure regions of the cardiovascular system, and are well placed to sense the blood volume in the
central thoracic compartment. These reflexes are thought to be particularly
important in controlling blood volume, as well as vascular tone, and act
together with the baroreceptors to stabilize the MABP. However, these reflexes
have been studied mainly in animals, and their specific individual roles in
humans are incompletely understood.
1 Atrial mechanoreceptors with non-myelinated
vagal afferents which respond to increased atrial volume/pressure by causing
bradycardia and vasodilatation.
2 Mechanoreceptors in the left ventricle and
coronary arteries with mainly non-myelinated vagal afferents which respond to
increased ventricular diastolic pressure and afterload by causing a
vasodilatation.
3 Ventricular chemoreceptors which are stimulated
by substances such as bradykinin and prostaglandins released during cardiac
ischaemia. These receptors activate the coronary chemoreflex. This
response, also termed the Bezold Jarisch effect, occurs after the
intravenous injection of many drugs, and involves marked bradycardia and
widespread vasodilatation.
4 Pulmonary mechanoreceptors, which when activated
by marked lung inflation, especially if oedema is present, cause tachycardia
and vasodilatation.
5 Mechanoreceptors with myelinated vagal
afferents, located mainly at the juncture of the atria and great veins, which
respond to increased atrial volume and pressure by causing a sympathetically
mediated tachycardia (Bainbridge reflex). This reflex also helps to
control blood volume; its activation decreases the secretion of antidiuretic
hormone (vasopressin), cortisol and renin, causing a diuresis. Although powerful in
dogs, this reflex has been difficult
to demonstrate in humans.
Chemoreceptor Reflexes
Chemoreceptors activated by hypoxia, hypocapnia and acidosis
are located in the aortic and carotid bodies. These are stimulated during
asphyxia, hypoxia and severe hypotension. The resulting chemoreceptor reflex
is mainly involved in stimulating breathing, but also has cardiovascular
effects. These include sympathetic constriction of (mainly skeletal muscle)
arterioles, splanchnic venoconstriction and a tachycardia resulting indirectly
from the increased lung inflation. This reflex is important in maintaining
blood flow to the brain at arterial pressures too low to affect baroreceptor
activity.
The CNS Ischaemic Response
Brainstem hypoxia stimulates a powerful generalized peripheral
vasoconstriction. This response develops during severe hypotension, helping to
maintain the flow of blood to the brain during shock. It also causes the Cushing
reflex, in which vasoconstriction and hypertension develop when increased
cerebrospinal fluid pressure (e.g. due to a brain tumour) produces brainstem
hypoxia.
Extrinsic Reflexes
Stimuli that are external to the cardiovascular system also exert effects
on the heart and vasculature via extrinsic reflexes. Moderate pain causes
tachycardia and increases MABP; however, severe pain has the opposite effects.
Cold causes cutaneous and coronary vasoconstriction, possibly precipitating
angina in susceptible individuals.
Central Regulation Of Cardiovascular Reflexes
The afferent nerves carrying impulses from cardiovascular receptors
terminate in the nucleus tractus solitarius (NTS) of the medulla.
Neurones from the NTS project to areas of the brainstem that control both parasympathetic
and sympathetic outflow, influencing their level of activation. The nucleus
ambiguus and dorsal motor nucleus contain the cell bodies of the
preganglionic vagal parasympathetic neurones, which slow the heart when the
cardiovascular receptors report an increased blood pressure to the NTS. Neurones
from the NTS also project to areas of ventrolateral medulla; from these
descend bulbospinal fibres which influence the firing of the sympathetic
preganglionic neurons in the intermediolateral (IML) columns of the spinal
cord.
These neural circuits are capable of mediating the basic cardiovascular
reflexes. However, the NTS, the other brainstem centres and the IML neurones
receive descending inputs from the hypothalamus, which in turn is influenced by
impulses from the limbic system of the cerebral cortex. Input from these higher
centres modifies the activity of the brainstem centres, allowing the generation
of integrated responses in which the functions of the cardio- vascular system
and other organs are coordinated in such a way that the appropriate responses
to changing conditions can be orchestrated.
