Short-term iv infusion of angiotensin II (AII) shifts or resets the baroreceptor reflex to a higher pressure level by a mechanism that is independent of the increase in arterial pressure. However, it is not known whether this acute resetting effect of AII persists when AII levels are chronically increased. Therefore, the purpose of this proposal is to test the general hypothesis that chronic increases in circulating AII in rabbits resets the baroreflex to a higher pressure level via a mechanism that is independent of pressure changes, and that this resetting contributes to the long-term regulation of blood pressure during AII-induced hypertension and during states of extracellular fluid depletion. Rabbits will be instrumented with aortic and vena caval catheters that can be attached to a swivel/tether system that permits constant infusion of AII. Baroreflex function will be assessed by examining the relationship between arterial pressure and heart rate or renal sympathetic nerve activity, and between arterial pressure and plasma concentrations of vasopressin and catecholamines, over a range of pressure levels (baroreflex function curves). We will test the hypothesis, first, by determining if the baroreflex function curves are shifted or reset to a higher pressure level during a two-week iv infusion of AII, even if the hypertensive effect of AII is acutely prevented by simultaneous iv infusion of nitroprusside. We will also determine whether the resetting is reversed when the All infusion is discontinued, even if the hypertension is maintained by iv infusion of phenylephrine. A final experiment will test the hypothesis that increased endogenous AII levels support sympathetic activity in states of extracellular fluid depletion by determining if blockade of the renin-angiotensin system decreases renal sympathetic nerve activity in sodium or water deprived rabbits. These studies will provide much needed information about the role of chronic elevations in AII in the regulation of blood pressure and baroreflex function, and also the role of AII in the genesis and maintenance of the hypertensive state.
