Reflex control of the circulation

Sensory receptors

 Arterial baroreceptors
 Cardiac receptors
 Arterial chemoreceptor
 Muscle metaboreceptors

Definition of reflexes

Excitatory inputs e.g. arterial chemoreceptors, muscle metaboreceptors stimulate

pressor responses. Pressor responses increase CO, TPR and BP

Inhibitory inputs e.g. arterial baroreceptors, cardiac-pulmonary receptors (pressure

receptors in the atria, ventricles and pulmonary arteries) stimulate depressor
responses. Depressor responses decrease CO, TPR and BP

Arterial baroreceptors

Baro means pressure so baroreceptors detect changes in pressure. Baroreceptors

respond to stretch. A rise in arterial pressure stretches the artery wall which deforms
and excites the receptors.

Blood flow and arterial baroreceptors

Arterial baroreceptors are vital to maintain blood flow to the brain and myocardium.
Monitoring blood pressure tells us about blood flow.

Blood pressure and arterial

baroreceptors

Lowering blood pressure means that

CO or TPR has decreased. So, blood
pressure indicates the blood flow.

Pa=CO x TPR
Blood flow(CO)=Pa/TPR

Location of baroreceptors

Baroreceptors are found in the adventitia of the carotid sinus and the aortic arch.
The carotid sinus is a thin walled dilation where the common carotid artery bifuactes
into the internal and external carotid arteries.

Afferent sensory fibres from the carotid sinus baroreceptors form the carotid sinus
nerve. The carotid sinus nerve joins the glossopharyngeal nerve and terminate in the
NTS
Afferent sensory fibres from the aortic baroreceptors join the vagus nerve and
terminate in the NTS.

Baroreceptors have dynamic and static sensitivity

Arterial baroreceptors respond to the magnitude of pressure (static sensitivity) and

its rate of change (dynamic sensitivity). If the carotid sinus is distended rapidly in an
experiment, the baroreceptors fire many action potentials at a high frequency. Then
the firing frequency decreases until it stabilises at a lower but still raised frequency.
When pressure is reduced, the baroreceptors fire action potentials at a low
frequency then falls to a lower rate.

In long term hypertension or hypotension, the baroreceptors adapts to the high

pressure so the threshold for firing rises or falls.

Effect of increased blood pressure on baroreflex

Stimulation of baroreceptors is called loading

Pulse pressure falls (decreased SV)

Vasodilation which decreases TPR and BP
Decreased sympathetic nerve activity
Increased vagus nerve activity

Effect of decreased blood pressure on baroreflex

Decreased stimulation of baroreceptors is called unloading (eg haemorrhage)

Increased sympathetic activity
Decreased vagus activity
Increased HR and force of contraction so CO increases
Constriction of the arterioles increases TPR
Vasoconstriction of arterioles decreases capillary pressure which increases
absorption of interstitial fluid. This increases blood volume
Venous constriction increases CVP so SV and CO increase by Starling’s law

This all maintains blood pressure and blood flow to vital organs

Central role of the nucleus tractus solitarius (NTS)

The NTS is a group of neurons. The
cardiovascular afferents, metaboreceptors,
mechanoreceptors, chemoreceptors and
pulmonary stretch receptors terminate in the
NTS. The processing of sensory information
begins in the NTS. The NTS receives many
different inputs so the output is influenced by
many different signals. This is called sensory
integration. The integrated information is relayed
by the NTS neurons to other regions.

Increased blood pressure

Increased blood pressure increases the stretch

of the aortic arch and carotid sinus.

Baroreceptors in aortic arch and carotid sinus

are stimulated. So vagus nerve and
glossopharyngeal nerve are stimulated.

The afferent activity from the arterial

baroreceptors is sent to the NTS through the
glossopharyngeal nerve and vagus nerve.

The NTS relays information to the nucleus

ambiguus (vagal nuclei). The nucleus
ambiguus contains vagal preganglionic neurons innervating the heart. There is
an increase in the activity of these vagal preganglionic neurons. This has a
depressor effect on the heart.

The NTS relays information to the cardiac vagal motorneurons (CVM) in the caudal
ventrolateral medulla (CVLM).

The CVLM sends inhibitory information to presympathetic neurons in the RVLM.

CVM and presympathetic neurons control parasympathetic and sympathetic

nerve activities respectively.

Inhibitory information to presympathetic neurons in the RVLM results in the inhibition

of sympathetic pre and post ganglionic neurones to the heart and vessels. So,
sympathetic innervation to the heart decreases which results in decreased HR,
vasoconstriction and BP.

Decreased blood pressure

Decreased blood pressure, decreases the stretch of aortic aortic and carotid sinus.
Decreased stimulation of the baroreceptors

There is decreased outflow from vagal preganglionic neurons of the nucleus

ambiguus
Inhibitory information to pre-sympathetic neurons in the RVLM is reduced so results
in activation of sympathetic pre and post ganglionic neurons to the heart and blood
vessels. So sympathetic innervation to the heart increases which results in increased
HR, vasodilation and BP.

Experimental link between CVLM and RVLM-1

Intravenous phenylephrine (a1 agonist) which increases TPR and blood pressure

BP rises and stretches/loads the baroreceptors

Signal from baroreceptor to NTS then CVLM

CVLM signals to inhibit RVLM signals

Sympathetic activity to the heart decreases so vasodilation occurs and BP

decreases.

Experimental link between CVLM and RVLM-1

Electrical stimulation of the CVLM decreases RVLM activity. This reduces the blood
pressure

Inhalation and the nucleus ambiguus

Inhalation switches off the nucleus ambiguus so HR increases.

Cardiac receptors

 Venoatrial mechanoreceptors (in right atrium and vena cavae)

Signal CVP and filling pressure of heart in diastole.

Stimulated by an increase in cardiac filling/CVP
An increase in cardiac blood volume stretches the veno atrial receptors.

Bainbridge effect: reflex tachycardia due to rapid infusion of saline into venous
system. The response is mediated partly by veno atrial stretch receptors and
pacemaker distension. Rise in right atrial pressure is detected by venoatrial
receptors. Increasing the heart rate serves to decrease the pressure in the superior
and inferior vena cavae by drawing more blood out of the right atrium.

Diuresis (increased production of urine) and natriuresis (increased salt excretion)

decreases plasma volume and lowers atrial distension. Diuresis is caused by a fall in
sympathetic activity to the kidneys causing renal vasodilation and changes in
circulating levels of ADH, Angiotensin II, aldosterone and ANP.

 Ventricular mechanoreceptors
Are stimulated by the over distention of the left ventricle and atria. The activity of the
left ventricular mechnoreceptors is weak unless the heart is distended. Atrial
mechanoreceptors only fire Aps when atrial volume is at its highest. The reflex is
weak but protects the heart from too much preload by causing mild vasodilation and
decreased blood pressure.

 Sympathetic nociceptors that are pain receptors.

Their fibre endings are chemosensitive so they can be activated by adenosine,

bradykinin, prostaglandins, histamine, 5-hydroxy-tryptamine, platelet released
thromboxane, lactic acid, K+ and reactive oxygen species. These are substances
released by ischaemic myocytes.

Referred pain occurs when activation of nociceptors in the viscera results in

feeling pain on the body surface. The nociceptive afferents travel to the spinal
cord in the cervical spinothalamic tract where they converge with somatic
afferents. So, a neuron receives input from nociceptors and somatic afferents.
So cardiac pain is felt from the chest wall, shoulders and arms. This is known
as referred pain.

The reflex increases sympathetic activity which causes person to be pale, sweaty,
tachycardia, angina/MI symptoms.

Arterial chemoreceptors

Located in the carotid and aortic bodies

Stimulated by arterial hypoxaemia (low PaO2)

Hypercapnia (high PCO2)
Acidosis
Hyperkalemia
Hypotension
Anaemia

They are well supplied with blood (20 ml/g/min)

The chemoreceptor afferent fibres travel in the vagus and glossopharyngeal nerves

Stimulate pressor response so…

 Peripheral resistance increases
Vasodilation of arterioles in skeletal muscle, renal etc. due to an increase
sympathetic activity
 Splanchnic veins constrict which supports central venous pressure
 Blood pressure rises
Due to TPR increasing and splanchnic veins constricting
 Tachycardia
An indirect consequence of increased breathing
The chemo reflex stimulates deeper and more rapid breathing which stimulates
stretch receptors in the lungs. This causes a lung inflation reflex which results in
tachycardia.
  Increase CO and BP especially to preserve cerebral blood flow

Chemoreceptors regulate alveolar ventilation and drive cardiac reflexes during

asphyxia (low O2 and high CO2), shock (systemic hypotension) and haemorrhage.

Asphyxia (hypoxaemia and hypercapnia occur during asphyxia)

Asphyxia stimulates arterial chemoreceptors very strongly causing a reflex rise in

sympathetic activity and blood pressure

Clinical shock

Caused by hypovolemia (ie due to severe haemorrhage), hypotension and

circulatory failure. Carotid and aortic body perfusion falls. Chemoreceptors are
excited by stagnant hypoxia and metabolic acidosis. The reflex causes rapid
breathing and increases TPR.

When BP drops below the baroreflex threshold, chemoreceptors will be still

active and will compensate.

Muscle metaboreceptors

The sensory fibres are in group IV motor fibres and are located in skeletal muscle

Stimulated by metabolites. Why? they are chemosensitive so are activated by

chemicals released by contracting muscle fibres. Ie ATP, K+, H2O4-, prostaglandin,
PGE2, bradykinin, lactic acid, adenosine.

Stimulate a pressor response

Increase blood pressure forces blood into contracted muscle and maintains muscle
perfusion
They also increase sympathetic vasomotor activity.
Increase contractility of the heart at high levels fo activity
Increase arterial and venous constriction
Increase CO and BP

When muscles are contracted, it restricts the blood flow in muscle. Metabolites also
accumulate to a high level.

Metabolites accumulate to a higher level during isometric (static) exercise compared

to dynamic exercise because isometric contraction restricts local blood flow. In static
exercise, muscle length and joint angle do not change. Examples of isometric
exercise are weight lifting and handgrip.

Vasoconstriction raises arterial blood pressure without decreasing flow because

metabolic vasodilation occurs to a greater extent.

Human metaboreceptors in static exercise

A local anaesthetic is injected that blocks metaboreceptors fibres in the muscle to
prevent pressor response. The subject maintained hand grip exercise. HR and BP
increased to a lesser extent.

Sinus tachycardia (sinus arrhythmia)

In inspiration, there is slightly less vagal activity so HR increases. During

expiration, the vagal activity decreases so HR decreases.

Limbic stimulation of cardiac vagal activity

The limbic system (emotional centre of the brain) stimulates the nucleus ambiguus.
This causes an increase in the activity of the vagus nerve so HR decreases. This
can lead to fainting (syncope, vasovagal) caused by decreased cerebral blood flow
(reduced oxygen delivery) due to a sudden drop in CO and blood pressure.

Cardiovascular afferents: stabilising blood pressure

Normally arterial blood pressure is fairly constant, and it is around 100mmHg. A fall
to 50mmHg could cause insufficient perfusion to end organs. Whereas, a rise to
150mmHg, could damage the CVS. When afferent fibres are removed, the average
BP is higher, but the range of blood pressures was large.