EXTRAVASCULAR HORMONAL ACTION OF ANGIOTENSIN II

最近观察到人血小板具有血管紧张素II（AII）， 受体促使我们研究这些血小板AII受体是否 在促进增强的血小板聚集中具有生理活性。 我们 初步研究表明，生理浓度的AII 显著增强肾上腺素诱导的血小板聚集。 血小板 在聚集计中定性测量聚集， 通过测定在以下情况下产生的血栓素B2的量来定量地测定 富含血小板的血浆与AII预孵育，然后与 肾上腺素 我们在这里提出的项目中的目标包括：（1） 研究AII对肾上腺素诱导的血小板聚集的影响， 凝血酶、胶原蛋白和ADP等;（2）研究其细胞机制， AII增强血小板聚集;（3）确定这是否增强 高血压患者的血小板聚集率高于血压正常者 患者;（4）研究饮食钠摄入量变化的影响 在这种增强的血小板聚集，鉴于事实上， AII受体随着高钠摄入而增加，反之亦然。 这些拟议研究的重要性与以下方面的重要性有关： 高血压是加速动脉粥样硬化主要原因 社会 因为有令人信服的证据表明血小板和AII 参与动脉粥样硬化病变的发展，详细 研究AII在促进血小板聚集中的作用可能最终 为动脉粥样硬化的发病机制提供了新的见解。

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.