High blood pressure is epidemic among the American population; it is estimated that in excess of 30 million people are afflicted with hypertension and another 20 to 30 million suffer from borderline hypertension. Our work has focused on understanding the operation of the RAS, especially the roles of angiotensin converting enzyme (ACE) and the biology of the angiotensin II receptor. During the last four years, we have studied the regulated expression of ACE and the receptor for angiotensin II. Our desire has been twofold, to understand the biochemical control mechanisms that the RAS uses to respond to environmental change and to understand tissue specific expression of the individual components of this system. We believe these questions are central to the workings of the RAS, and thus are of major importance in blood pressure control. In the present application, we propose to continue study of ACE expression and to focus on endothelium as a tissue central to RAS action. Finally, we propose to extend these studies into understanding how the RAS responds in a well defined model of hypertension. We propose to study a model of high renin hypertension in the rat induced by surgical banding of the abdominal aorta. This model has a well defined pathophysiology; we hypothesize that part of the pathophysiologic responses to hypertension in this model are the result of changes in components of the renin-angiotensin system. Analysis of the model will allow us to correlate the observation of Specific Aims 1 (the study of ACE by the kidney and vascular smooth muscle) and Specific Aim 2 (the study of ACE expression by endothelial cells) with an in vivo example of hypertensive injury. Thus, we will investigate tissue specific gene expression and use this to understand hypertensive injury.
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