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.
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