LEUKOTRIENES, PROSTACYCLIN, BLOOD VESSELS, HYPERTENSION

该研究计划涉及调查自然发生的因素或 控制和调节花生四烯酸（AA）释放的药剂和 AA代谢为前列环素（PGI 2）或血栓素（TxA 2）的主要途径 完整和受损的血管 对释放事件的进一步调查， PGI 2在循环中的最终命运将与 可能的生理机制，在调节血压，控制 血管反应性和血小板聚集。 牛肠系膜血管的组织切片和亚细胞组分或 将使用正常和高血压大鼠的动脉进行酶的研究 （磷脂酶A2、环氧合酶、前列环素合成酶和血栓素） 合成酶），其密切参与PGI 2的生物合成。 因素 或代理（例如，血管紧张素I和II，缓激肽），这可能会调节 将内过氧化物（PGG 2或H2）转化为PGI 2或TxA 2， 研究了 PGI 2和TxB 2的代谢将在体外进行研究， 以及在离体灌注的正常和 用~ 3 H标记的PGI_2或TxB_2为底物，对高血压大鼠的血压模型进行了研究。 代谢物 将血管中的PGI_2和TxB_2分离并通过GC-MS检测。 调节主要代谢酶的因子或试剂 （15-OH-前列腺素脱氢酶; 9-OH-前列腺素脱氢酶和 PGE-9-酮还原酶）。 这些建议旨在研究PGI 2的控制和调节， 血栓素的生物合成，它们的释放和代谢命运。 结果进行 研究将用于涉及PGI 2的生物合成和代谢的障碍， 正常和受损血管中的TxA 2和其他肾上腺素及其 与高血压的关系

The research proposal concerns investigation of factors or naturally occurring agents which control and modulate the release of arachidonic acid (AA) and the major metabolic pathway of AA to prostacyclin (PGI2) or thromboxane (TxA2) in the intact and damaged blood vessels. Further investigation of the release and the ultimate fate of PGI2 in the circulation will then be related to the possible physiological mechanism in the regulation of blood pressure, control of vascular reactivity and platelet aggregation. Tissue slices and subcellular fractions of bovine mesenteric blood vessels or normal and hypertensive rat aortas will be used for studies of the enzymes (phospholipase A2, cyclo-oxygenase, prostacyclin synthetase and thromboxane synthetase) which are intimately involved in the biosynthesis of PGI2. Factors or agents (e.g., angiotensins I and II, bradykinin) which may modulate the transformation of endoperoxides (PGG2 or H2) to PGI2 or TxA2 will be investigated. The metabolism of PGI2 and TxB2 will be studied both in vitro as well as in isolated perfused mesenteric blood vessels from normal and hypertensive rats using 3H-labeled PGI2 or TxB2 as substrate. The metabolites of PGI2 and TxB2 in blood vessels will be isolated and examined by GC-MS. Factors or agents which modulate the major metabolic enzymes (15-OH-prostaglandin dehydrogenase; 9-OH-prostaglandin dehydrogenase and PGE-9-ketoreductase) will also be investigated. These proposals are designed to study the control and regulation of PGI2 and thromboxane biosynthesis, their release and metabolic fate. Results of these studies will be used to relate disorders of biosynthesis and metabolism of PGI2, TxA2 and other prostaglandins in normal and damaged blood vessels and their relationship to hypertension.