Essentials of Blood Pressure Regulation in Hypertension

1. Essentials of Blood Pressure Regulation in Hypertension Dr. Thomas Abraham PHAR 417: Fall 2005

2. Blood Pressure Regulation in Hypertension Population dynamics of Hypertension and related pathologies • 60,000,000 Americans have one or more forms of cardiovascular disease (2002) • Hypertension is prevalent in about 35% of the adult population (50,000,000). • Coronary heart disease: 12, 600, 000 • Stroke: 4, 600, 000 • Cardiovascular disease claimed almost 800 000 lives in 1999; nearly twice as many as cancer, 10 times as much as accidents and about 60 times as much as AIDS (1997) • In 2002 Cardiovascular disease is estimated to cost the nation $330 billion in healthcare costs. • As the population ages these statistics are expected to increase.

3. Blood Pressure Regulation in Hypertension • Blood pressure influenced by: • 1. Peripheral vascular resistance which in turn is controlled by: • - vessel diameter; vasoconstriction/vasodilation • - blood viscosity; changes in hematocrit, osmolarity • - total vessel length; effects of fat tissue and weight loss. • Vessel elasticity • - Stiffening of arteries due to arteriosclerosis decreases vessel compliance and lumen pressure during pulsatile blood flow. • - Decreases with age. • Blood volume • - Increases in volume cause sustained increases in systemic pressure. • - Short-term changes in volume produced by decreased venous pooling • - Long-term changes controlled by the kidneys. • Cardiac Output • - amount of blood ejected by the heart per cycle maintains the pressure in the circulation.

4. Blood Pressure Regulation in Hypertension Short-term Blood Pressure Regulation : I. By changes in vessel (arteriolar) diameter Largest systemic pressure drop occurs in the arteriolar beds thus this is the region with the greatest resistance to blood flow. Changing the lumen diameter in these vessels will also influence the systemic blood pressure the greatest. Thick layer of muscular tunica media in arteries and arterioles allows for rapid change in vessel lumen diameter in response to sympathetic nerve stimulation or blood-borne hormone.

5. Blood Pressure Regulation in Hypertension • Autonomic control of blood pressure • Most arteries and some veins receive nerve inputs from postganglionic sympathetic neurons, with arteries and arterioles being more densely innervated. • Cardiovascular centers in the medulla oblongata initiate tonic sympathetic discharge that is transmitted down the spinal cord, via the presynaptic fibers and chain ganglia to the vasculature. Thus release of norepinephrine within the wall of arteries is responsible for activating a1-adrenoceptors to cause vasoconstriction.

6. Blood Pressure Regulation in Hypertension • Autonomic Regulation of BP: • Epinephrine (and some NE) released from adrenal medulla during sympathetic activation thought to activate the a2-adrenoceptor, which is more densely localized on the lumenal side of the smooth muscle layer. • Tissue metabolites (lactic acid, prostaglandins) and increasing PCO2 (decreasing PO2) can cause vasodilation of arterioles and venules to increase tissue blood flow.

7. Blood Pressure Regulation in Hypertension II. By changes in heart rate and contractility Mean Arterial Pressure = Total Peripheral Resistance X Cardiac Output Influenced by vessel diameter Influenced by cardiac function Changes in TPR or CO or both can influence the mean blood pressure in an individual. Generally sympathetic nervous system activation results in alteration of both parameters while various drugs may have selective effects on one or the other. (Pulse Pressure) MBP = DBP + 3 Pulse Pressure = Systolic Pressure – Diastolic Pressure

8. Blood Pressure Regulation in Hypertension Cardiac Output = Heart Rate X Stroke Volume Stroke volume is related to myocardial contractility therefore increasing contractile force of the heart increases stroke volume. Both stroke volume and heart rate influence the amount of blood the heart delivers per cardiac cycle to the circulatory system (cardiac output). b-adrenoceptor agonists directly increase the rate and contractility of the heart to influence the CO of the heart.

9. Blood Pressure Regulation in Hypertension Baroreceptor control of short-term Blood Pressure • Baroreceptors are stretch receptors found in the walls of the carotid sinus and the aortic arch that detect changes in arterial pressure. • Increases in blood pressure cause distention of the baroreceptors leading to increased rate of firing of afferent sensory nerves that eventually inhibit the tonic firing of the sympathetic motor center in the medulla.

10. Blood Pressure Regulation in Hypertension Autonomic Reflex Arc:

11. Blood Pressure Regulation in Hypertension

12. Blood Pressure Regulation in Hypertension The baroreceptor reflex is concerned with maintenance of the mean blood pressure. Drugs that cause increases in MBP initiate the reflex to bring down the pressure. The opposite would occur if vasodilatory drugs were administered or if MBP suddenly fell. Decrease in heart rate may be due to activation of baroreceptors leading to increased PNS activity and decreased SNS activity. Decreased baroreceptor stimulation with ISO may lead to increased SNS activity to increase HR and force. BP Phenylephrine 10 ug/kg Force Prazosin 1 ug/kg HR 3

13. Blood Pressure Regulation in Hypertension Long-term Blood Pressure Regulation ØMainly achieved by the regulation of blood volume by the kidneys. ØThe Renin-Angiotensin-Aldosterone axis for volume regulation: oChanges in blood volume due to sustained blood loss are detected by the Macula Densa cells of the kidneys as a decrease in Na+ in the glomerular filtrate. oJuxtaglomerular cells of the kidneys are stimulated to release renin into the blood which converts angiotensinogen to angiotensin I.

14. Blood Pressure Regulation in Hypertension • Renin-Angiotensin-Aldosterone axis: • oAngiotensin I is converted to angiotensin II by angiotensin- converting enzyme (ACE) found on endothelial cells. • oAngiotensin II is a potent vasoconstrictor that helps maintain the falling blood pressure. • oAngiotensin II also releases aldosterone from the adrenal cortex, which causes increased Na+ and water reabsorption from the distal convoluted and collecting tubules.

15. Blood Pressure Regulation in Hypertension

16. Blood Pressure Regulation in Hypertension • ØAnti-diuretic hormone (Vasopressin) and control of blood volume: • oIncreases in blood osmolarity are detected by the pituitary to cause release of ADH into the blood. • oADH is a vasoconstrictor that helps maintain blood pressure. • oADH increases water reabsorption in the DCT and collecting ducts of the kidneys. • oADH stimulates the thirst centers of the hypothalamus to increase water intake.

17. Blood Pressure Regulation in Hypertension • Etiology and Pathology of Hypertension • Less than 15% of hypertension cases have any identifiable causes (secondary hypertension): aortic coarctation, renal artery constriction, Cushing’s syndrome, pheochromocytoma, primary aldosteronism. • Common findings in essential hypertension (of unknown cause) include vascular smooth muscle hypertrophy, cardiac ventricular hypertrophy, decreased vessel compliance (stiffening) and increased arterial tone.

18. Blood Pressure Regulation in Hypertension • Etiology and Pathology of Hypertension • Risk factors associated with hypertension: heredity, race, gender, age, high salt diet, obesity, smoking and physical inactivity. • Untreated hypertension can result in atherosclerosis, stroke, myocardialinfraction, cardiac hypertrophy, arrhythmias, congestive heart failure, renal failure. • Blood pressure consistently above 150/95 requires pharmacological intervention while the presence of one or more risk factors may demand therapy at a lower threshold.