THROMBOXANE IN SEVERE HYPERTENSION

血栓烷是花生四烯酸的代谢产物，具有血小板聚集作用， 和血管收缩特性，当 血小板被刺激聚集。 我们在年轻人身上的初步发现 患有遗传性高血压的动物向我们表明， 血栓素在高血压中的潜在作用。 这使我们 推测血栓素可能在高血压发生中起重要作用 当存在血管损伤时，例如在严重的高血压中。 增强 血管血小板沉积后血栓素形成， 纤维素样坏死的发生可能会导致进一步的血压 升高和血管损伤以及相关并发症，如中风 和肾功能障碍 为了验证我们的假设血栓素是 与严重高血压的血压显著升高有关， 及其后遗症，研究将在SHRSP（遗传模型） 和肾动脉之间的主动脉完全结扎的大鼠（a 血栓素治疗的严重高血压动物模型 合成酶抑制剂、血栓烷受体拮抗剂或化学稳定的 前列环素模拟物。 水和电解质平衡，动脉收缩期 将在治疗组和对照组中测量血压和尿iTxB2。 未处理的有意识动物。 类似的研究将在 假手术进行主动脉结扎和WKY的动物。 血小板和 将进行肾功能研究以及血液测量 血栓素和血管花生四烯酸代谢水平， 处理和未处理的动物。 这些研究将评估 在严重高血压的发展中血栓素的产生增加 及其后遗症，并可能提供洞察到新的模式， 男性的抗高血压治疗。

Thromboxane is a metabolite of arachidonic acid having platelet aggregatory and vasoconstrictor properties and is generated in large amounts when platelets are stimulated to aggregate. Our preliminary findings in young animals with genetic hypertension have suggested to us that there is an underlying role of thromboxane in hypertension. This has led us to hypothesize that thromboxane may play an important hypertensinogen role when vascular damage is present such as in severe hypertension. Enhanced thromboxane formation subsequent to the vascular platelet deposition and fibrinoid necrosis which occurs may lead to further blood pressure elevation and vascular damage and associated complications such as stroke and kidney dysfunction. To test our hypothesis that thromboxane is involved in the marked elevation of blood pressure in severe hypertension, and its sequelae, studies will be performed in both SHRSP (a genetic model) and rats with complete ligation of the aorta between the renal arteries (a surgically-induced model of severe hypertension) treated with thromboxane synthase inhibitors, thromboxane receptor antagonists or chemically stable prostacyclin mimetics. Water and electrolyte balance, systolic arterial pressure, and urinary iTxB2 will be measured in both treated and non-treated conscious animals. Similar studies will be carried out in animals which are sham operated for aortic ligation and WKY. Platelet and renal functional studies will be performed as well as measurements of blood levels of thromboxane and vascular arachidonic acid metabolism in both treated and non-treated animals. These studies will evaluate the role of enhanced thromboxane production in the development of severe hypertension and its sequelae and may provide insights into newer modes of antihypertensive therapy in man.