EXTRAVASCULAR HORMONAL ACTION OF ANGIOTENSIN II

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The recent observation that human platelets possess angiotensin II (AII) receptors prompted us to study whether these platelet AII receptors were physiologically active in promoting enhanced platelet aggregation. Our preliminary studies demonstrated that physiological concentrations of AII significantly enhanced epinephrine-induced platelet aggregation. Platelet aggregation was measured qualitatively in an aggregometer and quantitatively by assaying the amount of thromboxane B2 generated when platelet rich plasma was preincubated with AII, and then incubated with epinephrine. Our objectives in the projects proposed here consist of: (1) studying the effect of AII on platelet aggregation by epinephrine, as well as thrombin, collagen, and ADP; (2) studying the cellular mechanism of this AII enhanced platelet aggregation; (3) determining whether this enhanced platelet aggregation is greater in hypertensive versus normotensive patients; and (4) studying the effect of changes in dietary sodium intake on this enhanced platelet aggregation, in light of the fact that platelet AII receptors increase with high sodium intake, and vice versa. The importance of these proposed studies is related to the importance of hypertension as a major cause of accelerated atherosclerosis in our society. Since there is compelling evidence that both platelets and AII are involved in the development of atherosclerotic lesions, a detailed study of the role of AII in promoting platelet aggregation may ultimately provide fresh insight into the pathogenesis of atherosclerosis.