VASOACTIVE HORMONES AND BLOOD PRESSURE REGULATION

这项建议侧重于在正常血压和高血压大鼠中，与血管运动控制的外周机制有关的血管血红素-血红素加氧酶-一氧化碳系统的功能和调节。四个主要的假设将被检验。首先，血红素加氧酶衍生的一氧化碳是由血管来源的小一氧化碳以张力方式制造的，它抑制小动脉和小动脉的肌源性行为和对收缩激素的反应。第三，血红素-血红素加氧酶-一氧化碳系统参与了外周降压机制的实施。第四，血红素-血红素加氧酶-一氧化碳系统有助于外周降压机制的实施。第四，血管紧张素依赖型高血压大鼠动脉组织中的高氧化应激促进了血管中血红素加氧酶产物的产生，而这反过来又削弱了适应性抗高血压和抗氧化功能。在测试这些假说时，以下特定目标将在正常血压和高血压大鼠中得到解决。目的1：从血红素加氧酶(S)的蛋白水平和一氧化碳的生成活性及能力来表征动脉血管中的血红素-血红素加氧酶系统的状态。我们将在正常血压和高血压大鼠的小动脉和大血管制造一氧化碳的能力以及血红素加氧酶蛋白和活性方面进行比较。目的2：明确血管血红素加氧酶产物的形成对血管收缩功能的影响。我们将研究增加或降低血管血红素-血红素加氧酶系统活性的干预措施对小动脉和小动脉的肌源性反应和对收缩激动剂的反应性的影响。目的：观察改变血红素加氧酶产物形成的干预措施对正常血压大鼠和自发性高血压大鼠血压的影响。我们将检测降低(血红素加氧酶抑制物；血红素加氧酶反义寡核苷酸)血红素加氧酶活性或血压表达水平的干预措施的血流动力学反应。目的：探讨血管紧张素依赖性高血压大鼠血管血红素加氧酶产物的形成与氧化应激的关系。我们将探讨抗氧化剂对高血压大鼠血管血红素-血红素加氧酶系统的影响以及血红素加氧酶抑制剂对氧化应激指标的影响。

This proposal focuses on the function and regulation of the vascular heme-heme oxygenase-carbon monoxide system in relation to peripheral mechanisms of vasomotor control in normotensive and hypertensive rats. Four major hypotheses will be examined. First, heme oxygenase-derived carbon monoxide is manufactured tonically, by small monoxide of vascular origin inhibits myogenic behavior and responsiveness to constrictor hormones in arterioles and small arteries. Third, the heme- heme oxygenase-carbon monoxide system contributes to the implementation of peripheral anti-hypertensive mechanisms. Fourth, the heme-heme oxygenase-carbon monoxide system contributes to the implementation of peripheral anti-hypertensive mechanisms. Fourth, high oxidative stress in arterial tissues of rats with angiotensin-dependent hypertension promotes vascular production of heme oxygenase products which, in turn, subserve adaptive anti-hypertensive and anti-oxidative functions. In testing these hypotheses, the following the following specific aims will be addressed in normotensive and hypertensive rats. AIM 1: To Characterize the Status of the Heme-Heme Oxygenase System of Arterial Vessels in Terms of Heme Oxygenase(s) Protein Level and Activity and Ability to Manufacture Carbon Monoxide. We will contrast small and large arterial vessels of normotensive and hypertensive rats in terms of ability to manufacture carbon monoxide and levels heme oxygenase protein and activity. AIM 2: To Define the Influence of Vascular Heme Oxygenase Product Formation on Vasomoter Function. We will examine the effect of interventions that increase or decrease the activity of the vascular heme-heme oxygenase system on myogenic responses and reactivity to constrictor agonist in small arteries and arterioles. AIM 3: To Determine the Effect of Interventions that Alter Heme-Oxygenase Product Formation on the Blood Pressure on Normotensive Rats and Spontaneously Hypertensive Rats. We will examine the hemodynamic response to interventions that decrease (heme oxygenase inhibitor; heme oxygenase antisense oligodeoxynucleotides) heme oxygenase activity or level of expression on blood pressure. Aim 4: To Explore Relationships Between Vascular Heme Oxygenase Product Formation and Oxidative Stress in Rats with Angiotensin-Dependent Hypertension. We will explore the effect of anti-oxidants on the vascular heme-heme oxygenase system and of heme oxygenase inhibitors on indices of oxidative stress in hypertensive rats.