LEUKOTRIENES, PROSTACYCLIN, BLOOD VESSELS, HYPERTENSION

研究建议涉及因素或自然发生的调查 控制和调节花生四烯酸(AA)和 花生四烯酸代谢前列环素(PGI2)或血栓素A2(TXA2)的主要途径 完整和受损的血管。对释放和释放的进一步调查 PGI2在循环中的最终命运将与 调节血压、控制血压的可能生理机制 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部分 正常和高血压大鼠的主动脉将用于这些酶的研究。 (磷脂酶A2、环氧合酶、前列环素合成酶和血栓素 合成酶)，它们与PGI2的生物合成密切相关。因素 或药物(如血管紧张素I和II，缓激肽)，可调节 将内过氧物(PGG2或H2)转化为PGI2或TXA2 调查过了。PGI2和TxB2的代谢将在体外进行研究， 以及离体肠系膜血管的正常和 以~3H标记的PGI2或TxB2为底物的高血压大鼠。代谢物 血管中的PGI2和TxB2将被分离并用GC-MS进行检测。 调节主要代谢酶的因子或制剂 (15-羟基前列腺素脱氢酶、9-羟基前列腺素脱氢酶和 PGE-9-酮还原酶)也将被研究。 这些建议旨在研究PGI2和PGI2的控制和调节 血栓素的生物合成、释放和代谢命运。这些措施的结果 研究将用于与前列腺素I2的生物合成和代谢障碍有关， 正常和受损血管中的TXA2等前列腺素及其受体 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.