1. Hypertension Definition: Hypertension is that level of sustained systemic arterial pressure which results over time in end-organ damage, most commonly in the eyes, the brain, the heart, the kidneys and the vasculature. Incidence in US:- among induvidualis over the age of 35 years : 20-25% - over 60 years: 35-40%

2. Clinical Classification of Blood Pressure a Blood PressureCategory (mm Hg) Diastolic <85 Normal 85-89 High normal 90-104 Mild hypertension 105-114 Moderate hypertension  115 Severe hypertension Systolic b <140 Normal 140-159 Borderline isolated systolic hypertension  160 Isolated systolic hypertension a Modified from The 1988 Report of the Joint National Committee on Detection. Evaluation and Treatment of High Blood Pressure. Arch Int Med 148: 1023-1038, 1988 b When diastolic blood pressure <90 mm Hg.

3. Etiology 90-95% of hypertension in adults has no indentifiable cause:  primary or essential 5-10% Secondary

4. Principal Causes of Hypertension I. 1. Idiopathic (essential, primary) 2. Renal A. Renovascular stenosis 1. Fibromuscular dysplasia 2. Atherosclerotic B. Renal parenchymal disease C. Obstructive nephropathy

5. Principal Causes of Hypertension II. Adrenal A. Medullary-pheochromocytoma B. Cortical 1. Primary aldosteronism a. Adrenal adenoma b. Bilateral adrenal hyperplasia 2. Cushing’s disease

6. Principal Causes of Hypertension III. Exogenous agents A. Oral contraceptives B. Sympathetic amines ( decongestants ) C. Nonsteroidal anti-infammatory drugs D. High dose corticosteroid administration E. Disorders simulating mineralocorticoid excess 1. Licorice 2. Chewing tobacco

7. Principal Causes of Hypertension IV. Miscellaneous A. Coarctation of aorta B. Acute stress

8. Determinant of normal blood pressure Myocardial Plasma Humoral Adrenergic Arteriolar function volume factors activity muscle tone Heart rate Na + balance catecholamines α-constriction autoregulation contractility aldosterone angiotensin II. β- dilatation cell Ca 2+ stroke volume kinins prostagladins CARDIAC PERIPHERAL VASCULAR OUTPUT RESISTANCE BLOOD PRESSURE

9. Pathogenetic Mechanisms in Secondary Hypertension Disorder Mediators Pathophysiologic Mechanisms Pheochromocytoma  Catecholamines Vasocontriction  Cardiac output Primary aldosteronism  Aldosterone Na + retention Renal artery stenosis  Renin a Vasoconstriction  Aldosterone Na + retention Renal insufficiency  GFR Na + retention  Renin a Vasoconstriction Cushing’s syndrome  Cortisol Na + retention  Renin substrate Vasoconstriction Oral contraceptives  Renin substrate Vasoconstriction Estrogen Na + retention Aortic coarctation  Renin Vasoconstriction  Aldosterone Na + retention a A minority of cases.

10. Essential Hypertension ( EH ) Thirty years ago, Page coined the term hypertension „mosaic”; his notion regarding the heterogeneity of hypertension remains highly relevant today. Factors contributing to the development of EH: 1. Systemic hemodynamics 2. Plasma volume 3. Renin-angiotensin system 4. Sympathetic nervous system 5. Kidney 6. Dietary factors sodium, calcium, potassium, obesity, alcohol 7. Heredity 8. Race

11. Effect of volume expansion on mean arterial pressure, cardiac output, and systemic vascular resistance in an anephric 22-year-old women From T. G. Coleman, H. J. Granger, and A. C. Guyton, Circ. Res., 28 (suppl. 2): 76, 1971

12. Inverse relationship between plasma volume (in: milliliters per centimeter of height) and diastolic blood pressure in untreated men with essential hypertension From H. P. Dustan, R. C. Tarazi, E. L. Bravo, and R. A. Dart, Circ. Res., 32 (suppl. 1): 73, 1973.

13. Direct relationship between diastolic blood pressure and plasma volume in 11 essential hypertensive patients during chronic diuretic treatment From H. P. Dustan, E. L. Bravo, and R. C. Tarazi, Am. J. Cardiol, 31:606, 1973.

14. Hemodynamic effects of the renin-angiotensin- aldosterone system Renal hypoperfusion  Afferent arteriolar stretch  NaCl delivery to macula densa  Renin release  Sympathetic neural tone Renin substrate Angiotensin I Angiotensin II. Converting enzyme  Aldosterone secretion  Renal Na + reabsorption Extracellular volume expansion  Systemic blood pressure  Renin release Hypotension Hypovolemia

15. Hemodynamic effects of the sympathetic nervous system  Effectivve circulating volume  Venous return  Cerdiac output  Blood pressure  Baroreceptor stimulation  Sympathetic tone Venous construction  Cardiac contractility Arterial construction  Renin secretion  Tubular Na + reabsorption  Venous return  Heart rate +  Vascular resistance  Angiotensin II formation  Cardiac output  Blood pressure  Aldosterone secretion  Effective circulating volume

16. Relationship between arterial blood pressure and urinary sodium chloride and water excretion in normal subjects and in patients with hypertension From A. C. Guyton, T. G. Colerman, a. W. Cowley, Jr. K. W. Scheel, R. D. Manning, Jr., and R. A. Norman, Jr., Am. J. Med., 52:584, 1972.

17. Effect of angiotensin II infusion in a dog in which renal artery pressure was initially servo-controlled at the baseline level Frrom J. E. Hall, J. P. Granger, R. L. Hester, T. G. Coleman, M. J. Smith, Jr., and R. B. Cross, Am. J. Physiol., 246:F627, 1984.

18. Action of plasma membrane Na + -K + -ATPase in the renal tubule and arteriolar smooth muscle

19. Correlation between mean arterial pressure and intracellular free calcium concentration in platelets From P. Erne, P. Bolli, E. Burgisser, and F. R. Buhler, N. Engl. J. Med., 310:1084, 1984.

20. Calcium The prevalence of EH appears to inversaly relates to dietary calcium intake with the risk rising two to three times as daily Ca intake falls from 1200 to less than 300 mg. There is, however, a direct correlation between mean arterial pressure and intracellular free calcium. Mechanism (?): Contradiction: extracellular Ca ++ intracellular Ca ++ Hypocalcemia could promote intracellular Ca cummulation (?)

21. Potasium In humans with EH K supplementation has been shown to produce a moderate fall in BP averaging 5 to 6 mmHg. Mechanism(?): - it acts mainly in Na sensitive patients - it may act in part by enhancing urinary sodium excretion

22. Obesity The incidence of hypertension is increased in obese patients - increase in plasma volume - sympathetic activity enhanced - SVR higher - insulin resistance  increased Na retention ( insulin  increase Na-K-ATP ase activity, increased insulin resistance and secretion  Na-K- ATP ase  )

23. Alcohol 1 or 2 drink a day  1.5 to 2 times as likely to become hypertensive Mechanism: plasma volume  ; NE  ; renin  ; Na-excretion 

24. Others Smoking, coffeine (?) Heredity and Race 70-80 % of patients with EH have a positive family history Correlation's within families between parents and children's medium, identical twins, (high) adopted children (low)