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.
Wei
Shun-Guang
SG
Research Service, Veterans Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
Felder
Robert B
RB
D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology; D002339:Carotid Arteries; D003714:Denervation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007668:Kidney / Q000294:innervation*; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D016548:Prosencephalon / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D000803:Angiotensin I; D002216:Captopril