application) The goal of this proposal is to increase our understanding of the effect of glucocorticoids on neural control of the circulation. Normal plasma glucocorticoid concentrations are necessary for arterial pressure homeostasis. This is evident in conditions of glucocorticoid insufficiency, which produce hypotension, and in how glucocorticoids modulate neural control of the circulation. Sympathetic nerve activity is a primary regulator of arterial pressure, and angiotensin II (ANG II) increases sympathetic activity through several mechanisms. Therefore, the present project will test the following hypotheses: 1) glucocorticoids increase sympathetic nerve activity and HR, and they attenuate baroreflex control of these variables, and 2) the actions of glucocorticoids on sympathetic outflow, HR and blood pressure are mediated, at least in part, by facilitation of the central actions of ANG II. As a correlate to this, it is also hypothesized that long-term treatment with an angiotensin receptor antagonist can attenuate the development of glucocorticoid- induced hypertension. To test these hypotheses the following specific aims will be achieved: 1) the effects of normal and elevated plasma corticosterone (cort) concentrations on baroreceptor reflex control of HR and renal sympathetic nerve activity (RSNA) will be determined in conscious rats: in these experiments, the effect of cort on resting levels of arterial pressure, RSNA and HR will also be assessed; 2) the contribution of central angiotensinergic mechanisms to the effects of cort on the regulation of arterial pressure, HR and RSNA will be determined in conscious rats by acute intracerebroventricular administration of either ANG II or the combined (AT1 and AT2) ANG II receptor antagonist, [sar1thr8]angiotensin II; and 3) the total contribution of both central and peripheral angiotensinergic mechanisms to glucocorticoid hypertension will be determined by long-term administration of Losartan, an orally available angiotensin receptor antagonist. In these experiments, arterial pressure and HR will be monitored continuously by radiotelemetry. All the work will be conducted in conscious rats, and increases in cort will be produced by exogenous administration. The results will provide fundamental new knowledge of the mechanisms of glucocorticoid-mediated modulation of arterial pressure regulation.