VASOACTIVE HORMONES AND BLOOD PRESSURE REGULATION

该建议的重点是正常血压和高血压大鼠血管血红素加氧酶-一氧化碳系统的功能和调节，与血管扩张控制的外周机制有关。将检验四个主要假设。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紧张性地制造的，抑制肌生成行为和对小动脉和小动脉中收缩激素的反应。第三，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，血管紧张素依赖性高血压大鼠动脉组织中的高氧化应激促进血管血红素加氧酶产物的产生，这反过来又有助于适应性抗高血压和抗氧化功能。在测试这些假设时，将在血压正常和高血压大鼠中解决以下具体目标。目标1：从血红素加氧酶蛋白水平和活性以及产生一氧化碳的能力方面表征动脉血管血红素-血红素加氧酶系统的状态。我们将对比血压正常和高血压大鼠的大小动脉血管制造一氧化碳的能力和血红素氧合酶蛋白和活性水平。目的2：明确血管血红素氧合酶产物的形成对血管运动功能的影响。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中肌源性反应和收缩激动剂反应性的影响。目标3：确定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。我们将检查血流动力学反应的干预措施，减少（血红素加氧酶抑制剂;血红素加氧酶反义寡核苷酸）血红素加氧酶活性或表达水平对血压。目标4：血管紧张素依赖性高血压大鼠血管血红素氧合酶产物形成与氧化应激的关系我们将探讨抗氧化剂对血管血红素-血红素加氧酶系统的影响，以及血红素加氧酶抑制剂对高血压大鼠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.