1. 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 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.

2. Part 1: Quick acting Autonomic Reflexes that maintain arterial pressure SENSORS Baroreceptors Carotid sinus Aortic arch Atria Vena cava Chemoreceptors Peripheral Aortic body Carotid body change Output Sympathetic Parasympathetic hormonal 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.

3. Carotid sinus pressure response Arterial pressure, mm Hg Impulses/sec carotid sinus nerve 80100120140160 180 Aortic archCarotid 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.

4. 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 Vagus & glossopharyngeal nerves Vascular baroreceptors Arterial input to vasomotor area Central input to vasomotor area

5. 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. inhibition Vasodilator 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

6. Baroreflex  sympathetic tone  secretion of NaCl & H 2 O 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 pressure MAP = CO x TPR +  venous pressure  venous return CO = HR x SV IX, X

7. Pressure range of baroreceptors Carotid sinus60 to 180 mm Hg Aortic arch90 to 210 mm Hg Peripheral chemoreceptors Below 80 mm Hg CNS ischemic response below 60 mm Hg Maximal 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, PCO 2 and PO 2 ; at low arterial pressure they potentiate vasoconstriction & stimulate respiration. Increased respiratory rate aids in venous return.

8. 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  PCO 2 in vasomotor center

9. 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.

10. Continuous vasoconstrictor tone from the vasomotor center maintains arterial pressure. Spinal block via injection of anesthetic blocks sympathetic tone from medulla Arterial pressure decreases ~ 50% Norepinephrine can still elicit a constriction (vessels are responsive) Quadriplegia Arterial pressure is unstable, heart rate decreases, stroke volume increases Minutes Arterial pressure, mm Hg 150 125 100 75 50 25 Sympathetic block Norepinephrine I.V. 0510152025 Sympathetic blockade decreases AP by ~ 50%

11. Cutting the baroreflex nerves makes the arterial blood pressure unstable. controlno baroreflex

12. 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  receptors Dilation in skeletal muscle epinephrine

13. Postprandial hypotension in autonomic insufficiency 80 100 120 60 40 20 140 160 Minutes after a standard test meal MAP, mm Hg 9060300 90603009060300 Healthy youngHealthy oldAutonomic failure  MAP = -25 mm Hg MAP before test meal

14. 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

15. 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 activity Gut metabolism Gut hormones  resistance skeletal muscle TPR decreases, MAP decreases

16. 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

17. 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 -

18. Intrinsic pressure diuresis in an isolated artificially perfused kidney Perfusion pressure pressure Na + excretion 100 80 120 1 2 3 4 5 In an isolated kidney only intrinsic mechanisms function; nerves have been severed and circulating hormones are not present

19. Pressure diuresis versus renal function curve Arterial blood pressure 10080120 1 2 3 4 5 Na + excretion 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

20. Hormones that affect renal Na + reabsorption shift the pressure diuresis curve ANP   Na+ excretion Arterial blood pressure 10080120 1 2 3 4 5 Na + excretion (times normal) 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.

21. Short and long-term control of arterial pressure Short 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 Thirst Aldosterone Vasopressin