ROLE OF PRESSOR PROSTANOIDS IN HYPERTENSION

这是一个研究血管收缩剂参与的建议， 前列腺素类在促高血压机制中的作用 我们建议激活 血管TXA 2/PGH 2受体通过类花生酸类，而不是TXA 2参与 内皮依赖性血管收缩的介导和 高血压的机制。 以下目标将在 正常血压大鼠和血管紧张素依赖性和非依赖性大鼠 高血压的形式。 1. 血管收缩剂的表征 血管组织通过内皮依赖性释放类花生酸 机制等 生物测定和HPLC技术将用于定量和 根据色谱图、内皮依赖性 环加氧酶和血栓烷合酶合成的需要，和 TXA 2/PGH 2受体在实施血管收缩中的作用， 花生四烯酸从灌注的血管中释放的收缩物质 主动脉和肠系膜脉管系统。 2. 调查的刺激， 血管收缩剂类花生酸的内皮依赖性释放。 释放 血管收缩剂类二十烷酸在用各种试剂刺激期间将 在AIM 1中进行检查。 3. 评价类花生酸诱导的 TXA 2/PGH 2血管受体在激素介导下的激活- 引起血管收缩。 我们将对比血管反应， 各种激素在离体血管中灌注， TXA_2/PGH_2血管受体在EDRF介导的血管舒张中的作用 放松. 内皮依赖性和- 独立代理人将在存在和不存在的情况下进行研究 TXA 2/PGH 2拮抗剂，TXA 2所起的作用由类花生酸激活 TXA 2/PGH 2受体在血管紧张素依赖性和非血管紧张素依赖性脑血管病发生中的作用 高血压的独立形式。 我们将对比 TXA_2/PGH_2联合治疗对大鼠高血压影响 拮抗剂、TXA 2合成抑制剂或两种治疗的组合。

This is a proposal to investigate the participation of vasoconstrictor prostanoids in prohypertensive mechanisms. We propose that activation of vascular TXA2/PGH2 receptors by eicosanoids other that TXA2 participates in the mediation of endothelium-dependent vasoconstriction and in the mechanisms of hypertension. The following aims will be addressed in normotensive rats and in rats with angiotensin dependent and independent forms of hypertension. 1. Characterization of the vasoconstrictor eicosanoids released from vascular tissues via endothelium-dependent mechanisms. Bioassay and HPLC techniques will be used to quantitate and characterize in terms of chromatographic profile, endothelium dependency, requirement of cyclooxygenase and thromboxane synthase for synthesis, and role of TXA2/PGH2 receptors in the implementation of vascular contraction, the contractile material released by arachidonic acid from the perfused aorta and mesenteric vasculature. 2. Investigation of the stimuli for endothelium-dependent release of vasoconstrictor eicosanoids. The release of vasoconstrictor eicosanoids during stimulation with various agents will be examined as in AIM 1. 3. Evaluation of the role of eicosanoid-induced activation of TXA2/PGH2 vascular receptors in the mediation of hormone- induced vasoconstriction. We will contrast the vascular responses to various hormones in isolated vasculatures perfused with and without TXA2/PGH2 vascular receptors in attenuation of EDRF-mediated vascular relaxation. The vasodilatory effect of endothelium-dependent and - independent agents will be studied in the presence and the absence of TXA2/PGH2 antagonists, TXA2 of the role played by eicosanoids that activate TXA2/PGH2 receptors in the development of angiotensin-dependent and - independent forms of hypertension. We will contrast the development of hypertension in rats with and without concurrent treatment with TXA2/PGH2 antagonists, TXA2 synthesis inhibitors, or both treatments combined.