This Hypertension SCOR will utilize a multidisciplinary approach to study the etiology, therapy, and complications of hypertension and the role which humoral factors factors play in these processes. One important objective will be to delineate the role of the renin-angiotensin system in experimental and clinical hypertension and the clinical usefulness of long-term angiotensin blockade. We plan to characterize the importance of sodium and volume factors in hypertensive states and to study their interaction with peripheral sympathetic activity, vasoactive hormones, cardiovascular function, and the renal kallikrein-kinin system. We will attempt to identify new mineralocorticoid hormones that could influence the development of hypertension in man and to determine the cause of low renin hypertension. We will study human alpha and beta adrenergic receptor activity in model system using circulating blood cells, and will assess the relationship of such receptor binding to plasma catecholamines, adrenergic responses, and antihypertensive therapy. We also will examine the effects of tyrosine and other amino acids on blood pressure and sympathetic activity in order to develop new therapeutic approaches for both hypertension and orthostatic hypotension. The influence of hypertension and its therapy on vascular and cardiac complications also will be investigated. These studies will focus in part on the mechanisms by which hypertension induces vascular injury in both arteries and arterioles and the effects of various treatments on the prevention on reversal of this process. We also will characterize the influence of hypertension and its treatment on the metabolism of arteries and cerebral micro-vessels and will study in detail the properties and regulation of angiotensin I converting enzyme. Treatment of congesive heart failure by angiotensin I blockade will be studied both in conscious dogs and man. Finally, we hope to clarify the role of the renin-angiotensin system in the regulation of regional and systemic vascular resistance in experimental animals with coronary occlusion and in patients with peripheral vascular disease. These studies should provide important insights into the pathogenesis and complications of hypertension and lead to improved approaches for its prevention and therapy.
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