Brain angiotensin-converting enzyme activity and autonomic regulation in heart failure

1 Department of Internal Medicine, University of Iowa, and 2 Veterans Affairs Medical Center, Iowa City, Iowa 52242 Submitted 3 February 2004 ; accepted in final form 29 June 2004 Several recent studies suggest an important role for the brain renin-angiotensin system in the pathogenesis of heart failure. Angiotensin-converting enzyme (ACE) activity and binding of angiotensin type 1 (AT 1 ) receptors, which mediate the central effects of ANG II, are increased in heart failure. The present study examined the relationship between brain ACE activity and the autonomic dysregulation characteristic of rats with congestive heart failure. Rats with heart failure (HF) induced by coronary artery ligation and sham-operated control (SHAM) rats were treated with chronic (28 days) third cerebral ventricle [intracerebroventricular (ICV)] or intraperitoneal (IP) infusion of a low dose of the ACE inhibitor enalaprilat (ENL) or vehicle (VEH). VEH-treated HF rats had increased sodium consumption, reduced urine sodium and urine volume, and increased sympathetic nerve activity with impaired baroreflex regulation. These responses were minimized or prevented by ICV ENL started 24 h after coronary ligation. IP ENL at the low dose used in these studies had no beneficial effects on HF rats. Neither IP nor ICV ENL had any substantial effect on the SHAM rats. The findings confirm a critically important contribution of the brain renin-angiotensin system to the pathophysiology of congestive heart failure. cardiovascular; neurohumoral; volume regulation; sympathetic activity; forebrain Address for reprint requests and other correspondence: R. B. Felder, Univ. of Iowa College of Medicine, E318-GH, 200 Hawkins Dr., Iowa City, IA 52242 (E-mail: robert-felder{at}uiowa.edu )