EICOSANOID MEDIATED PRESSOR MECHANIMS IN HYPERTENSION

这是一项研究其作用机制和对血压影响的建议。 二十烷基类化合物介导的升压与血压关系的调节 正常血压和高血压大鼠的血管降压功能。研究是 在两个相关领域提出了建议。 L地区：血管对花生四烯酸代谢的影响 脂氧合酶(S)对前列腺素介导的血压机制的研究 监管-需要检验的假设是，过度的形成 脂氧合酶产物，推测为花生四烯酸过氧化氢，由 血管紧张素依赖性高血压大鼠的动脉血管 通过促进基因表达促进血压升高 PGH2介导的血管收缩机制并通过限制 前列腺素I2介导的血管扩张机制的活性。实验将是 在血管紧张素依赖性高血压大鼠(主动脉 缩窄性高血压；血管紧张素II输注诱导 高血压)，在血管紧张素非依赖性高血压(DOCA- 盐源性高血压)和相应的正常血压对照组。 在这些实验模型中，我们提出实验(A)以确定 并对正常血压和高血压患者血管组织中的脂氧合酶活性进行定量。 (B)探讨脂氧合酶与高血压大鼠的关系(S) 正常血压血管组织的产物形成和前列腺素I2的产生 和高血压大鼠；(C)调查 脂氧合酶(S)产物对高血压发病机制的研究 脂氧合酶(S)抑制对血压的影响及相关因素 高血压和正常血压大鼠的肾功能；(D)探讨 脂氧合酶抑制对血流动力学反应的影响 和PGI2介导的血管降压系统的活性；(E)检查 脂氧合酶产物的形成与表达的关系 前列腺素H2介导的小动脉血管收缩机制 正常血压和高血压大鼠。 区域2：细胞色素P450对花生四烯酸代谢的影响 加氧酶对正常血压和高血压大鼠血压的影响 需要检验的假设是2O-HETE有助于增加血液 幼年自发性高血压大鼠和其他自发性高血压大鼠模型的压力和血管反应性 20-HETE合成高表达的高血压。实验 将在自发性高血压大鼠中进行，通过治疗使大鼠高血压 DOCA-盐或地塞米松，并在相应的正常血压下 控制。在这些模型中，我们提出了实验(A)来研究 20-HETE合成抑制剂治疗对系统性红斑狼疮的影响 正常血压大鼠、自发性高血压大鼠和自发性高血压大鼠的血流动力学及相关肾功能 其他形式的实验性高血压；(B)探讨20- HETE在血管对收缩激素反应性调节中的作用 正常血压和高血压大鼠。

This is a proposal to study the mechanisms and impact on blood pressure regulation of relationships between eicosanoid-mediated pressor and vasodepressor functions in normotensive and hypertensive rats. Research is proposed in two related areas. AREA l: The Influence of Arachidonic Acid Metabolism by Vascular Lipoxygenase(s) on Prostanoid-Mediated Mechanisms of Blood Pressure Regulation - The hypothesis to be tested is that excessive formation of lipoxygenase products, presumably arachidonic acid hydroperoxides, by the arterial vessels of rats with angiotensin-dependent hypertension contributes to the elevation of blood pressure by fostering the expression of a vasoconstrictor mechanism mediated by PGH2 and by limiting the activity of a vasodilatory mechanism mediated by PGI2. Experiments will be conducted in rats with angiotensin-dependent hypertension (aortic coarctation-induced hypertension; angiotensin II-infusion-induced hypertension), in rats with angiotensin-independent hypertension (DOCA- salt-induced hypertension) and in the corresponding normotensive controls. In these experimental models we propose experimentation (a) to identify and quantify lipoxygenase activity in vascular tissues of normotensive and hypertensive rats; (b)to examine the relationship between lipoxygenase(s) product formation and PGI2 production by vascular tissues of normotensive and hypertensive rats; (c) to investigate the contribution of lipoxygenase(s) products to mechanisms of hypertension by determining the consequences of lipoxygenase(s) inhibition on blood pressure and relevant renal functions of hypertensive and normotensive rats; (d) to explore relationships between the hemodynamic response to lipoxygenase inhibition and the activity of vasodepressor systems mediated by PGI2; (e) to examine the relationship between lipoxygenase product formation and the expression of PGH2-mediated mechanism of vasoconstriction in small arterial vessels of normotensive and hypertensive rats. AREA 2: The Influence of Arachidonic Acid Metabolism by Cytochrome P450 Oxygenases on the Blood Pressure of Normotensive and Hypertensive Rats - The hypothesis to be tested is that 2O-HETE contributes to increase blood pressure and vascular reactivity in young SHR and in other models of hypertension in which 20-HETE synthesis is hyperexpressed. Experiments will be conducted in SHR, in rats made hypertensive by treatment with DOCA-salt or with dexamethasone, and in the corresponding normotensive controls. In these models we propose experimentation (a) to investigate the effect of treatment with an inhibitor of 20-HETE synthesis on systemic hemodynamics and relevant renal functions in normotensive rats, SHR and other forms of experimental hypertension; (b)to explore the role of 20- HETE in regulation of vascular responsiveness to constrictor hormones in normotensive and hypertensive rats.