VASCULAR AT1A RECEPTOR ROLE IN BLOOD PRESSURE CONTROL

血管紧张素II(AII)1a型受体(AT1a)位于血管、肾脏和中枢神经系统(CNS)，对动脉血压的控制和AII诱导的高血压的病理起着至关重要的作用。血管AT1a和CNS AT1a对这一调控的不同贡献尚不清楚。我们假设血管AT1a在基础血压调节和AII诱发高血压的病理过程中起重要作用。为了测试这一点，AT1a将分别置于平滑肌(SMC)和内皮细胞(EC)启动子SM22pha和Tie2的控制下，以产生在这些血管组织中过度表达AT1a的转基因小鼠。转基因将被转移到AT1a基因敲除背景上，得到的小鼠的AT1a只位于血管系统中。使用生理学和药理学技术，将检查基础血压和对急性和慢性注射AII的血压反应。此外，使用分离的主动脉和颈动脉节段，将评估对AII的等长收缩反应。此外，这些小鼠模型将有助于研究氧化应激在AII介导的高血压中的作用。这些实验的结果将使我们能够进一步描述在缺乏中枢介导的AII反应的情况下，SMC和EC中的AT1a在调节基础血压和AII介导的高血压中的作用。

Angiotensin II (AII) type 1a receptors (AT1a), located in the vasculature, kidney, and central nervous system (CNS), are crucial for the control of arterial blood pressure (BP) and the pathology of AII induced hypertension. The differential contributions of vascular and CNS AT1a to this regulation is poorly understood. We hypothesize that vascular AT1a significantly contribute to basal blood pressure regulation and the pathology AII induced hypertension. To test this, AT1a will be placed under the control of smooth muscle (SMC) and endothelial cell (EC) promoters, SM22alpha and Tie2, respectively, in order to generate transgenic mice over expressing AT1a in these vascular tissues. The transgenes will be transferred onto an AT1a knockout background with the resulting mice having AT1a located only in the vasculature. Using physiological and pharmacological techniques, basal BP and BP responses to acute and chronic infusions of AII will be examined. Also, using isolated aortic and carotid artery segments, the isometric contractile responses to AII will be evaluated. Moreover, these mouse models will be useful for investigating the contribution of oxidative stress that is observed in AII mediated hypertension. The results of these experiments will allow us to further delineate the contribution of AT1a in SMC and EC to the regulation of basal BP and AII mediated hypertension in the absence of centrally mediated AII responses.