HIGH SALT DIET, ANGIOTENSIN II, AND MICROVESSEL DILATION

描述（改编自申请人摘要）：高盐饮食 内容在西方社会很常见，长期以来一直被认为是一种风险 高血压的因素。从历史上看，人们认为高盐 饮食导致盐敏感个体血压升高， 动脉压的升高会导致 血管功能然而，最近的研究表明，高盐摄入量也 影响正常血压动物的血管结构和反应性， 改变是通过血管紧张素II（ANG II）抑制介导的。这些新颖 重要的观察结果具有重要的临床意义，因为它们 表明，受损的血管扩张反应报告在许多形式的 盐敏感性高血压可能不依赖于血压的升高。 这就提出了一种可能性，当与其他诱发因素相结合时， 因素，改变血管反应性与盐摄入量增加可能导致 盐敏感性高血压的发展。该项目将利用 分离的、插管的阻力动脉和原位微循环 准备测试中心假设，即盐摄入量增加本身 导致小动脉和阻力动脉中血管舒张反应性受损 正常血压动物，这种作用是通过抑制 ANG II.本研究的具体目的是：1）确定是否 高盐饮食引起的血管舒张受损是由于 血管平滑肌细胞的改变、内皮细胞的改变 功能，或两者兼而有之; 2）评估电生理机制的作用 在导致动物对血管扩张刺激的反应受损的作用中， 高盐饮食; 3）确定血管紧张素Ⅱ和特异性血管紧张素Ⅱ受体的作用 亚型在维持高盐动物正常血管舒张反应中的作用 饮食.阐明血管反应性改变的机制， 在高盐饮食动物的小动脉和阻力动脉中， 增加了对ANG II在调节 在不存在升高的干扰效应的情况下的血管舒张反应 动脉压

DESCRIPTION (Adapted from the applicant's abstract): Diets with high salt content are common in Western society, and have long been implicated as a risk factor for hypertension. Historically, it has been believed that the high salt diet leads to an elevated blood pressure in salt sensitive individuals, and that this elevation in arterial pressure leads to pathological alterations in vessel function. However, recent studies suggest that elevated salt intake also affects vessel structure and reactivity in normotensive animals, and that these alterations are mediated via angiotensin II (ANG II) suppression. These novel and important observations have substantial clinical implications, since they demonstrate that the impaired vasodilator responses reported in many forms of salt sensitive hypertension may not depend on the elevation of blood pressure. This raises the possibility that, when combined with other predisposing factors, altered vascular reactivity with elevated salt intake could lead to the development of salt sensitive hypertension. This project will utilize isolated, cannulated resistance arteries and in situ microcirculatory preparations to test the central hypothesis that elevated salt intake per se leads to impaired vasodilator reactivity in arterioles and resistance arteries of normotensive animals, and that this effect is mediated via suppression of ANG II. The specific aims of this study are: 1) to determine whether the impaired vascular relaxation occurring in response to high salt diet is due to alterations in the vascular smooth muscle cells, alterations in endothelial function, or both; 2) to evaluate the role of electrophysiological mechanisms in contributing to the impaired response to vasodilator stimuli in animals on a high salt diet; 3) to determine the role of ANG II and specific ANG II receptor subtypes in maintaining normal vasodilator responses in animals on a high salt diet. Elucidating the mechanism of the altered vascular reactivity that occurs in arterioles and resistance arteries of animals on a high salt diet can lead to an increased understanding of this novel role of ANG II in regulating vasodilator responses in the absence of the confounding effects of elevated arterial pressure.