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）：H2O 酶促降解血红素，产生一氧化碳 (CO)。 CO 可以放松血管平滑肌。 这些研究将检验这样的假设：在 Angll 诱导的高血压期间 H2O2 介导的 CO 产生增加，并且它有助于部分保护肾血流动力学和心血管功能。 具体目标： 1) 确定在正常血压和 Angll 诱导的高血压大鼠中，HS 饮食是否会急性或慢性增强内源性 CO 诱导的利尿/尿钠排泄、增加心输出量和降低计算的肾血管阻力。 2)确定高原低盐饮食Angll诱导的高血压大鼠的心血管和肾脏HO蛋白表达及其氧化应激途径的改变。方法：将在急性麻醉和清醒的长期仪器正常血压和AngII输注的高血压大鼠中评估肾脏/全身血流动力学、排泄和组织学参数。通过给予血红素前体 DALA 和 H2O 抑制剂 ZnPP 来改变 CO 系统。目的：这些研究将确定 HO-CO 系统在 AngII 诱导的高血压中的作用。这些知识可能会带来治疗高血压的新治疗策略。