EFFECTS OF HYPERTENSION AND HYPERHOMOCYSTEINEMIA ON CEREBROVASCULAR FUNCTION

慢性高血压是颈动脉粥样硬化的主要危险因素 疾病和中风。 现在建议使用转基因技术进行研究。 小鼠和病毒介导的基因转移，以阐明 慢性高血压患者的脑血管功能改变 最近 有证据表明，高同型半胱氨酸血症也是一个主要的风险， 颈动脉疾病和中风的危险因素。 建议进行研究 探讨高同型半胱氨酸血症对脑血管的影响， 功能 研究人员计划验证这一假设， 高血压双转基因小鼠内皮功能障碍 (that过度表达肾素和血管紧张素原），并检查 内皮功能障碍的机制。 还建议进行研究 为了确定内皮NO合酶基因转移是否 （eNOS）改善卒中倾向患者的血管反应 高血压大鼠（SHRSP）的基底动脉和颈动脉。 如果 基因转移后血管功能改善，这将代表 基因转移技术在脑肿瘤中的首次“治疗性”应用 血管在疾病状态的实验模型中。 胱硫醚β-合酶（CBS）基因敲除小鼠发育 高同型半胱氨酸血症 计划进行研究，以确定是否 这是颈动脉和大脑的内皮功能障碍 高同型半胱氨酸血症（CBS敲除）小鼠的小动脉，如果 所以，研究一下这个机制。 在过去的几年里， 很清楚脑血中存在钾离子通道 血管，K+通道的激活是一个重要的 松弛机制。 计划进行研究， 假设对ATP敏感（K+）开放剂的反应 ATP）通道在高血压小鼠中受损。 研究是 他提出了一个假设，即与K + ATP相比， 钙离子依赖性钾通道功能活性 正通道在高血压转基因小鼠中增加， SHRSP。 血栓调节蛋白表达于内皮细胞， 结合凝血酶并激活蛋白C，一种有效的抗凝剂。 高同型半胱氨酸血症可抑制Thromobomodulin活性。 建议进行研究以检验血栓调节蛋白 在SHRSP和高血压转基因小鼠中活性降低。 这种抗凝机制的损害可能有助于 高血压易患中风。

Chronic hypertension is a major risk factor for carotid artery disease and stroke. Studies are ow proposed to use transgenic mice and viral-mediated gene transfer to clarify mechanisms of altered cerebral vascular function in chronic hypertension. Recent evidence suggests that hyperhomocysteinemia also is a major risk factor for carotid artery disease and stroke. Studies are proposed to examine effects of hyperhomocysteinemia on cerebral vascular function. The investigators plan to test the hypothesis that there is endothelia dysfunction in hypertensive double transgenic mice (that overexpress both renin and angiotensinogen), and to examine mechanisms of endothelial dysfunction. Studies are also proposed to determine whether gene transfer of endothelial NO synthase (eNOS) improves vascular responses in stroke-prone spontaneously hypertensive rats (SHRSP) in the basilar and carotid artery. If vascular function improves after gene transfer, this will represent the first "therapeutic" use of gene transfer technology for cerebral blood vessels in an experimental model of a disease state. Cystathionine beta-synthase (CBS) knockout mice develop hyperhomocysteinemia. Studies are planned to determine whether these is endothelia dysfunction in the carotid artery and cerebral arterioles of hyperhomocysteinemic (CBS knockout) mice and, if so, to examine the mechanism. During the past few years, it has become clear that K plus channels are present in cerebral blood vessels, and that activation of K plus channels is an important mechanism of relaxation. Studies are planned to test the hypothesis that responses to an opener of ATP-sensitive (K plus ATP) channels are impaired in hypertensive mice. Studies are proposed to test the hypothesis that, in contrast to K plus ATP channels, functional activity of Ca plusplus minus dependent K plus channels is increased in hypertensive transgenic mice and in SHRSP. Thrombomodulin, which is expressed on endothelium, binds thrombin and activates protein C, a potent anticoagulant. Thromobomodulin activity is inhibited by hyprhomocysteinemia. Studies are proposed to test the hypothesis that thrombomdulin activity is decreased in SHRSP and hypertensive transgenic mice. Impairment of this anticoagulant mechanism might contribute to susceptibility to stroke in hypertension.