AJP - Heart and Circulatory Physiology, Vol 269, Issue 2 425-H432, Copyright © 1995 by American Physiological Society

ARTICLES

Central angiotensin II AT1-receptor antagonism in normal and heart-failed sheep

M. T. Rademaker, M. A. Fitzpatrick, C. J. Charles, C. M. Frampton, A. M. Richards, M. G. Nicholls and E. A. Espiner
Department of Medicine, Christchurch Hospital, New Zealand.

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) type 1 (AT1)-receptor antagonist losartan (0.1 followed by 0.5 mg.kg-1.3 h-1) to six concious sheep before (nonpaced) and after induction of heart failure by rapid left ventricular pacing (paced). In both nonpaced 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) and 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 nonpaced 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.

This article has been cited by other articles:

				H. Murakami, J.-L. Liu, and I. H. Zucker Angiotensin II Enhances Baroreflex Control of Sympathetic Outflow in Heart Failure Hypertension, February 1, 1997; 29(2): 564 - 569. [Abstract] [Full Text]