FUNCTIONAL ANALYSIS OF VASCULAR ANGIOTENSIN II

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The purpose of this investigation is to determine the functional role of angiotensin II (AII) generated in the vasculature on systemic arterial pressure (BP), basal vascular tone and adrenergic reactivity. Stimuli responsible for the release of renin and AII from the intact vascular bed will be studied. Because of its highly reactive renin-angiotensin system and stable cardiovascular system during withdrawal of blood samples for the required assays, the rabbit will be utilized. Femoral artery perfusion pressure and BP will be monitored in pentobarbital anesthetized rabbits. A femoral venous shunt will allow for administration of captopril to the hindlimb without recirculating and thus allow for selective angiotensin converting enzyme inhibition. Nephrectomized and sham operated rabbits will be employed to compare the relative importance of AII formed in the hindlimb vasculature on basal parameters. In order to eliminate complications of nephrectomy on electrolyte balance and plasma urea and to further induce the influence of vasculature AII, the animals will undergo peritoneal dialysis before each experiment at 1, 2 and 4 days post op. Interventions to be studied on vascular renin and AII release will be beta 1 and beta 2-adrenoceptor stimulation, direct electrical stimulation of sympathetic nerves, hemorrhage, afferent nerve stimulation, changes in calcium and sodium and Goldblatt hypertension. The accompanying changes in BP, femoral vascular resistence and femoral vascular responses to adrengeric nerve stimulation and norepinehrine will be determined. Captopril and saralasin will be employed as a means of distinguishing the involvement of the vascular renin- angiotensin system during these intervetnions. Because of the postulated role of vascular AII in the regulation of BP and vascular tone in disease states such as hypertension and congestive heart failure and possibly under basal conditions, knowledge about this system is important.