Forebrain renin-angiotensin system has a tonic excitatory influence on renal sympathetic nerve activity

All elements of the renin-angiotensin system (RAS) are present in the forebrain, particularly in circumventricular organs surrounding the third cerebral ventricle. We tested the hypothesis that forebrain angiotensin-converting enzyme (ACE) has a tonic excitatory influence on sympathetic drive. Neurally intact and sinoaortic-denervated pentobarbital-anesthetized rats were treated with forebrain-directed intracarotid artery (ICA) versus intravenous injections of angiotensin I (ANG I) and of the ACE inhibitor captopril. In intact rats, ICA ANG I elicited a rise in arterial pressure and a concomitant reduction in renal sympathetic nerve activity (RSNA; ICA captopril elicited the opposite responses). In barodenervated rats, ICA ANG I increased and ICA captopril decreased arterial pressure and RSNA in parallel; intravenous ANG I had no effect on RSNA. The findings suggest that the intrinsic forebrain RAS has a tonic excitatory influence on sympathetic drive that is overshadowed in normal rats by baroreflex mechanisms, but may assume a more prominent role in pathophysiological states (e.g., heart failure) in which baroreflex mechanisms are impaired and RAS activity is augmented.