Outline: Regulation of arterial pressure

There is a critical requirement to maintain sufficient blood

pressure to perfuse the brain, heart & other vital tissues.

Blood pressure is maintained at normal levels by

Quick-acting autonomic reflexes and

Long term regulation by pressure diuresis

TPRxCOMAP

zeroCVPTPR

CVPMAPCO

R

PF

Mean arterial pressure is a function of cardiac output and total peripheral resistance.

Autonomic reflexes maintain MAP by responding to changes in pressure with

adjustments of CO and TPR.

Part 1: Quick acting Autonomic Reflexes that maintain arterial pressure

SENSORSBaroreceptors

Carotid sinusAortic archAtriaVena cavaChemoreceptorsPeripheralAortic bodyCarotid body

change

OutputSympatheticParasympathetichormonal

CNS (set point)

Feedback

Input

Carotid sinus nerve to glossopharyngeal n. (IX)

Carotid body

Common carotids

Vagus n. (X)

Aortic bodies

Aortic arch

Carotid sinus

The arterial baroreflex is the most important autonomic reflex maintaining MAP. This reflex can induce changes CO & TPR within seconds in response to a change in MAP.

Carotid sinus pressure response

Arterial pressure, mm Hg

Impu

lses

/se

c ca

rotid

sin

us

ner

ve

80 100 120 140 160 180

Aortic arch Carotid sinus

Vagus

CNS

Hering’s nerve

Glossopharyngeal

The baroreflex senses changes in arterial pressure as changes in diameter of the carotid sinus & aortic arch. An increase in diameter stretches mechanoreceptors in the walls of the vessels. The frequency of action potentials from the receptors is directly proportional to arterial pressure.

Afferent limb of the baroreflex

A2 Sensory area (nucleus tractus

solitarius)

Vasomotor center

(Medulla & Pons)

Anterior hypothalamus

Cerebral cortex

Posterior hypothalamus

Excitatory or inhibitory

Excitatory or inhibitory

Excitatory

Vagus & glossopharyngeal nerves

Vascular baroreceptors

Arterial input to vasomotor area

Central input to vasomotor area

Almost all small arteries, arterioles, venules & veins have sympathetic constrictor innervation. Changes in sympathetic activity can affect TPR.

Sympathetic nerves also carry vasodilator fibers to skeletal muscle.

inhibitionVasodilator area A1

Sino-atrial node (heart rate)

Vagus nerve

Dorsal motor nucleus

parasympathetic

Vasomotor center

(Medulla & Pons)

vasoconstriction

Vasoconstrictor area C 1

sympathetic

Efferent signals from the vasomotor center

Baroreflex

sympathetic tone

secretion of NaCl & H2O retaining hormones

cardiac output

HR contractility

Parasympathetic tone to heart

stroke volume

TPR

Venous mechanoreceptors(atria, vena cava near heart)

Central nervous system

blood volume Arterial blood pressure

arterial mechanoreceptors(carotid sinus,aortic arch)

Arterial blood pressureMAP = CO x TPR

+

venous pressure

venous returnCO = HR x SV

IX, X

Pressure range of baroreceptors

Carotid sinus

60 to 180 mm Hg

Aortic arch 90 to 210 mm Hg

Peripheral chemoreceptors

Below 80 mm Hg

CNS ischemic response

below 60 mm HgMaximal at 15 to 20 mm Hg

Carotid sinus afferents are most important in regulating arterial

pressure in the normal pressure range.

Chemoreceptors primarily regulate blood pH, PCO2 and PO2; at low arterial

pressure they potentiate vasoconstriction & stimulate respiration. Increased

respiratory rate aids in venous return.

CNS ischemic response

Blood flow to brain

Blood flow to vasomotor center

The CNS ischemic response is a “last-ditch” emergency response that

produces maximal increases in arterial pressure (up to 250 mm Hg).

The CNS ischemic response produces its maximal effect when arterial pressure is in the 15 to 20 mm Hg range.

Maximal stimulation of sympathetic outflow

PCO2 in vasomotor center

Venous blood reservoirs & baroreflex

The capacitance veins in the liver, lungs, spleen, intestines &

subcutaneous venous plexus constrict with sympathetic stimulation as

part of the baroreflex response to hypotension or hypovolemia.

Veins feeding into the superior vena cava do not participate in baroreflex

induced constriction.

Constriction of the capacitance veins transfers blood toward the heart.

Therefore these veins act as blood reservoirs.

Continuous vasoconstrictor tone from the vasomotor center maintains arterial pressure.

Spinal block via injection of anesthetic blocks sympathetic tone from medullaArterial pressure decreases ~ 50%Norepinephrine can still elicit a constriction (vessels are responsive)QuadriplegiaArterial pressure is unstable, heart rate decreases, stroke volume increases

Minutes

Art

eria

l pre

ssu

re, m

m H

g150

125

100

75

50

25

Sympathetic block

Norepinephrine I.V.

0 5 10 15 20 25

Sympathetic blockade decreases AP by ~ 50%

Cutting the baroreflex nerves makes the arterial blood pressure unstable.

control no baroreflex

Vasovagal syncope

Emotional disturbance (cerebral cortex)

TPR

arterial pressure

Vasodilator fibers to skeletal muscle

Spinal cord

Anterior hypothalamus

medullaVagus nerve

Brain blood flow

Fainting (syncope)

cardiac output

Heart rate

Adrenal medulla

breceptors

Dilation in skeletal muscle

epinephrine

Postprandial hypotension in autonomic insufficiency

80

100

120

60

40

20

140

160

Minutes after a standard test meal

MA

P, m

m H

g

9060300 9060300 9060300

Healthy young Healthy old Autonomic failure

D MAP = -25 mm Hg

MAP before test meal

Circulatory changes in the postprandial state in healthy young subjects

Maintenance of MAP via interaction of local metabolic effects with

changes in sympathetic tone is a general principle of circulatory

function.

Ingestion of a meal

Afferents from GI tract

CNS

Resistance in GI tract

Sympathetic activity

Sympathetic activity

Gut metabolism

Gut hormones

Resting resistance

skeletal muscle, skin

TPR maintained at normal level

Circulatory changes in the postprandial state in autonomic failure

Subjects with autonomic failure experience a large decrease in MAP after

a meal that may be accompanied by syncope due primarily to absence

of an increase in resistance in resting skeletal muscle, skin.

Ingestion of a meal

Afferents from GI tract

CNS

resistance in GI tract

Sympathetic activityGut metabolism

Gut hormones

resistance skeletal muscle

TPR decreases, MAP decreases

Use of the tilt table aids in determining the cause of syncope.

The two most common causes of postural hypotension are autonomic failure (which can be caused by multiple disorders) and volume depletion.

In autonomic failure hypotension causes

syncope because the decrease in AP is

not accompanied by the normal

baroreflex mediated increase in HR.

Passive head-up tilt causes maximal

dependent pooling of blood and

stresses the baroreflex response to

decreased central blood volume.

Normal

Part 2: Long term regulation by pressure diuresis

The pressure diuresis mechanism acts as a negative feedback connecting kidney function with blood pressure

Diuresis: urine flow

Natriuresis: Na+ excretion

Arterial pressure

Blood volume

Urine flow

Na+ excretion+

Na+ excretion

Blood volume

Urine flow

Arterial pressure

-

Intrinsic pressure diuresis in an isolated artificially perfused kidney

Perfusion pressure pressure

Na+

exc

retio

n

10080 120

1

2

3

4

5

In an isolated kidney only intrinsic mechanisms function; nerves have been severed and circulating hormones are not present

Pressure diuresis versus renal function curve

Arterial blood pressure

10080 120

1

2

3

4

5

Na

+ e

xcre

tion

Renal function curve

Intrinsic pressure diuresis curve

The renal function curves shows the effect of arterial pressure on Na+ excretion in the intact kidney with normal neural and hormonal function

Hormones that affect renal Na+ reabsorption shift the pressure diuresis curve

ANP Na+ excretion

Arterial blood pressure

10080 120

1

2

3

4

5N

a+ e

xcre

tion

(tim

es n

orm

al)

Atrial natriuretic peptide (ANP)

normal

angiotensin II

angiotensin II Na+ excretion

Hypertension is a renal disease

Angiotensin stimulates Na+ reabsorption, opposing pressure diuresis. Under angiotensin stimulation a higher blood pressure is needed to excrete the ingested NaCl. ANP has the opposite effect.

Short and long-term control of arterial pressureShort term

Fluid intake

Parasympathetic activity

TPR

Preload

Blood volume

Contractility

Frank-Starling mechanism

SVHR

CO

MAP

Fluid output (urine)

Pressure diuresis

Long term

Baroreceptors

CNS vasomotor center

Sympathetic activity

ThirstAldosteroneVasopressin