Endothelin Actions on Vascular Function in Hypertension

内皮素对高血压血管功能的作用

• 批准号: 7060772
• 负责人: RALPH E WATSON
• 金额: $ 16.52万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7060772
• 关键词: African American; angiotensin /renin /aldosterone hypertension; blood chemistry; caucasian American; clinical research; dietary sodium; endothelin; gene expression; hormone receptor; hormone regulation /control mechanism; human subject; laboratory rat; nutrition related tag; racial /ethnic difference; receptor expression; receptor sensitivity; superoxides; vasomotion

DESCRIPTION (provided by applicant): Dr. Watson's goal is to become an independent investigator focused on the vascular biology of hypertension (HT) and other cardiovascular diseases. Through a class on concepts and techniques in molecular biology, a class on statistical methods, several annual conferences, journal clubs, and hands on research in mentors' laboratories, he will acquire the necessary technical and analytical skills. The overall goal of the research project is to study how endothelin (ET-1) (a potent vasoconstrictor and growth stimulator) controls blood pressure. HT is more common and severe in African-Americans (AA), and the HT in this group is more often salt-sensitive. In animal models, continuous infusion of ET-1 causes sustained, salt-sensitive HT. In salt-sensitive animal models, ET-1 receptor antagonists lower blood pressure. ET-1 levels are more elevated in AA hypertensives (8-fold). Also, ET-1 receptors vary by race. Does ET-1 play a significant role in the development, maintenance, and complications in the HT in this population? Studies suggest that the ET-1 system in AA hypertensives is similar to that in animal models of salt-sensitive hypertension. Dr. Watson will start by studying ET-1 effects on arteries and veins in the Dahl salt-sensive rat, an excellent model of salt-sensitive HT. These studies have never before been performed in this model. Once he has mastered these techniques, he plans to study human arteries and veins by similar techniques, comparing AA and white hypertensives in novel ways. No one has compared the distribution of ET-1 receptors or the expression of the ET-1 gene in these populations. In the rat, he will study the contractile responses of mesenteric arteries and veins to ET-1; ET-1 levels, gene expression, receptor protein and gene expression in arteries and veins; measure superoxide anion in arteries and veins; determine the effect of chronic treatment with ET-1 receptor antagonists; and evaluate venomotor tone in vivo and effect of ET-1 receptor antagonists. In human tissue, he will compare contractile reactivity to ET-1, measure ET-1 gene expression, vascular superoxide levels, and possibly receptor levels in AA and white hypertensives. Could this lead to the development of a new class of ET-1 receptor antagonists for the treatment of salt-sensitive HT and the prevention of vascular complications of HT?

描述（由申请人提供）： 沃森博士的目标是成为专注于高血压血管生物学（HT）和其他心血管疾病的独立研究者。 通过关于分子生物学概念和技术的课程，统计方法，几个年度会议，期刊俱乐部以及指导者实验室研究的班级，他将获得必要的技术和分析技能。 研究项目的总体目标是研究内皮素（ET-1）（有效的血管收缩和生长刺激剂）如何控制血压。 HT在非裔美国人（AA）中更为普遍，更严重，并且该组中的HT通常对盐敏感。在动物模型中，连续输注ET-1会导致持续的盐敏感HT。在盐敏感的动物模型中，ET-1受体拮抗剂降低了血压。 AA高血压（8倍）中ET-1水平升高。 此外，ET-1受体因种族而异。 ET-1在该人群中HT的发展，维护和并发症中是否起着重要作用？研究表明，AA高血压中的ET-1系统与盐敏感高血压的动物模型相似。 Watson博士将首先研究ET-1对DAHL盐 - 溶剂大鼠中动脉和静脉的影响，Dahl盐 - 含量是盐敏感的HT的出色模型。 这些研究从未在此模型中进行。 一旦掌握了这些技术，他计划通过类似技术研究人类动脉和静脉，以新颖的方式比较AA和白色高血压。 没有人比较ET-1受体的分布或在这些人群中ET-1基因的表达。在大鼠中，他将研究肠系膜动脉和静脉对ET-1的收缩反应。 ET-1水平，基因表达，受体蛋白和基因表达在动脉和静脉中；测量动脉和静脉中的超氧阴离子；确定用ET-1受体拮抗剂慢性治疗的作用；并评估体内毒液张力和ET-1受体拮抗剂的作用。 在人体组织中，他将比较收缩反应性与ET-1，测量ET-1基因表达，血管超氧化物水平以及AA和白色高血压中的受体水平。 这是否会导致开发新的ET-1受体拮抗剂来治疗盐敏感的HT和预防HT的血管并发症？