BARORECEPTOR REFLEX INTERACTIONS WITH ANGIOTENSION

The purpose of this proposal is to investigate the interaction between arterial baroreceptor reflexes and the actions of angiotensin (II) on the central nervous system. Previous work by this applicant has indicated that conscious sinoaortic baroreceptor denervated rats are 3.6 times more sensitive to the pressor effects of intravenous bolus injection of angiotensin than are baroreceptor intact rats. In comparison, the baroreceptor denervated group was more than 1000 times more sensitive to the pressor effects of central (intracerebroventricular) angiotensin administration. The first specific objective of this study will be to more rigorously define the extent of this very marked inhibitory influence of the baroreflex on the central pressor actions of angiotensin. Experiments are proposed to determine: (1) if the potentiation persists during constant interacerebroventricular infusion of angiotensin, (2) the contribution of cardiac output versus peripheral resistance to the augmentation, (3) if the central actions of blood-borne angiotensin are augmented with baroreceptor denervation, (4) if the potentiation occurs with other centrally acting pressor agents, and (5) if a noncardiovascular action of central angiotensin, such as drinking, is affected by baroreceptor denervation. The second specific objective of this propsal will be to examine the influence of angiotensin on baroreflex function. This approach will examine the pressor sensitivity to continuous infusion of angiotensin in baroreceptor intact versus denervated animals and will include a comparison with baroreflex influences on pressor sensitivity to phenylephrine and vasopressin. The possible influence of angiotensin on baroreflex function will also be examined in anesthetized rats during simulated baroreceptor activation by electrical stimulation of the aortic depressor nerve while recording peripheral sympathetic nerve activity. As further test of the contribution of the central action of angiotensin, experiments will be repeated with a specific knife-cut in the anterior hypothalamus which eliminates the central pressor effects of angiotensin. These types of approaches will provide further understanding of neural circulatory control specifically relating to baroreflex influences on the central action of angiotensin and, conversely, the influence of angiotensin on baroreflex control of arterial pressure.