OXYGENASE METABOLITES AND RENAL VASCULAR ACTIVITY

加氧酶代谢物和肾血管活动

• 批准号: 6139280
• 负责人: John D Imig
• 金额: $ 9.3万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6139280
• 关键词: angiotensin /renin /aldosterone hypertension; angiotensin II; antihypertensive agents; arachidonate; eicosanoid metabolism; eicosanoids; enzyme activity; enzyme feedback; enzyme inhibitors; hormone regulation /control mechanism; kidney circulation; laboratory rat; lipoxygenase; microcirculation; muscle tone; nephrectomy; oxygenases; pathologic process; vascular smooth muscle; vasodilators; vasomotion; video microscopy

DESCRIPTION: (Adapted from the application) The overall hypothesis to be tested in this proposal is that increases in production of lipoxygenase metabolites and decreases in production of epoxygenase metabolites contribute to enhanced vascular tone of preglomerular vessels and elevation in blood pressure associated with increased circulating levels of angiotensin II. Rats will be prepared with chronic infusion of angiotensin II and the development of hypertension followed. At selected time intervals, the metabolites of epoxygenase and lipoxygenase will be measured. The reactivity of renal microvasculatures will be evaluated and assayed for the production of the various metabolites of arachidonic acid. In addition, in vitro juxtamedullary nephron techniques combined with video microscopy will be used to determine preglomerular vascular tone in vitro; the various contributions of metabolites lipoxygenase and epoxygenase will be assessed using pharmacological inhibition of these probes both in the acute and chronic situation. Results of these studies will further define the renin-angiotensin system and determine the role of arachidonic acid metabolism in the development of angiotensin-dependent hypertension.

描述：（从应用程序改编）总体假设为 在此提案中测试的是脂氧合酶的产生增加 代谢物并减少环氧酶代谢产物的产生 有助于增强的血管前血管和高程的血管张力 在与循环水平升高有关的血压中 血管紧张素II。 大鼠将通过长期输注血管紧张素来制备 II和高血压的发展随之而来。 在选定的时间 将测量间隔，环氧酶和脂氧合酶的代谢产物。 将评估和测定肾小管的反应性 产量蛛网膜酸的各种代谢产物。 此外， 体外并列肾脏技术与视频显微镜结合 将用于在体外确定前血管张力；各种 将评估代谢物脂氧合酶和环氧酶的贡献 在急性和 慢性情况。 这些研究的结果将进一步定义 肾素 - 血管紧张素系统并确定花生四烯酸的作用 血管紧张素依赖性高血压发展中的代谢。