Carbon monoxide in AngII dependent hypertension

AngII 依赖性高血压中的一氧化碳

• 批准号: 6934567
• 负责人: Keith E Jackson
• 金额: $ 5.15万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934567
• 关键词: NAD(P)H dehydrogenase; angiotensin /renin /aldosterone hypertension; angiotensin II; blood flow measurement; blood pressure; carbon monoxide; cardiovascular function; diuresis; enzyme activity; fatty acids; glomerular filtration rate; heart rate; heme oxygenase; hemodynamics; kidney function; laboratory rat; low salt diet; nitric oxide synthase; nutrition related tag; oxidative stress; oxidoreductase inhibitor; postdoctoral investigator; posttranslational modifications; protein isoforms; saluresis; vascular resistance

DESCRIPTION (provided by applicant): Enzymatic degradation of heme by HO yields carbon monoxide (CO). CO relaxes vascular smooth muscle. These studies will test the hypothesis that HO-mediated CO production is increased during Angll induced hypertension, and it contributes to partial protection of renal hemodynamic and cardiovascular function. Specific Aims: 1) Determine if endogenous CO induced diuresis/natriuresis, increased cardiac output and decreased calculated renal vascular resistance is acutely or chronically enhanced by HS diet in normotensive and Angll-induced hypertensive rats. 2) Determine cardiovascular and renal HO protein expression and its alterations by the oxidative stress pathway in Angll induced hypertensive rats on highland low-salt diets. Methods: Renal/Systemic hemodynamic, excretory, and histological parameters will be evaluated in anesthetized acutely and in awake chronically instrumented normotensive and Angll infused hypertensive rats. CO system wills altered by administration of a heme precursor, DALA, and a HO inhibitor, ZnPP. Objectives: These studies will establish the role of the HO-CO system in the Angll induced hypertension. This knowledge may lead to novel therapeutic strategies for treating hypertension.

描述（由申请人提供）：HO对血红素的酶促降解产生一氧化碳（CO）。 CO可以放松血管平滑肌。 这些研究将检验以下假设：HO介导的CO产生在Angll诱导的高血压期间增加，并有助于部分保护肾脏血流动力学和心血管功能。 具体目的：1）确定内源性CO诱导的利尿/纳地尿，心输出量增加以及计算出的肾血管耐药性降低是否会通过正常且呼吸诱导的高血压大鼠在HS饮食中急剧或长期增强。 2）确定心血管和肾HO蛋白表达及其通过Angll诱发高盐饮食中高血压大鼠的氧化应激途径的改变。方法：将在麻醉和清醒的长期仪器中，肾脏/系统性血流动力学，排泄和组织学参数进行评估。 CO系统的遗嘱通过施用血红素前体达拉和HO抑制剂Znpp改变。目标：这些研究将确定HO-CO系统在Angll诱发的高血压中的作用。这些知识可能会导致治疗高血压的新型治疗策略。