APStracts 2:0152H, 1995.

Central angiotensin ii at1-receptor antagonism in normal and heart failed sheep. Rademaker, M T, M A Fitzpatrick, C J Charles, Cm Frampton, Am Richards, Mg Nicholls, E A Espiner. Department of Medicine, Christchurch Hospital & The Christchurch School of Medicine, Christchurch, New Zealand.

APStracts 2:0152H, 1995.

The role of the brain renin-angiotensin system (RAS) in heart failure was examined by administering intracerebroventricular (ICV) infusions of the angiotensin II (Ang II) AT1-receptor antagonist, losartan (0.1 followed by 0.5 mg/Kg/3hrs), in six concious sheep before (non-paced) and after induction of heart failure by rapid left ventricular pacing (paced). In both non-paced and paced states, ICV losartan abolished drinking, induced a significant diuresis (p<0.05) and anti -natriuresis (p<0.05) and increased plasma renin activity (p<0.05), Ang II (p<0.01). and aldosterone levels (0.1>p<0.05). Plasma arginine vasopressin was suppressed by ICV losartan only in the paced state (p<0.05). Hemodynamics were not altered by ICV losartan in the non-paced animals. In the paced state, however, significant reductions in left ventricular systolic, mean arterial and left atrial pressures were observed (decrements of 13+7, 12+5 and 3.4+0.7 mmHg, respectively, all p<0.05). In conclusion, Ang II within the brain participates in the regulation of thirst and body electrolyte and fluid homeostasis in normal and heart failed sheep, and appears to play a role in regulating resting hemodynamic status in this model of heart failure.

Received 1 July 1994; accepted in final form 4 April 1995.
APS Manuscript Number H578-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.