Renal hemodynamics in rats with myocardial infarction: selective
antagonism of angiotensin receptor subtypes.
Mento, Peter F., Mary E. Maita, and Barry M. Wilkes.
Division of Nephrology and Hypertension, Department of Medicinem,
North Shore University Hospital, and the Department of Medicine,
Cornell University Medical College, Manhasset, New York
APStracts 3:0209H, 1996.
Rats with congestive heart failure demonstrate striking intrarenal
vasoconstriction that contributes to reduced renal excretory
function. The importance of specific angiotensin II receptor subtypes
(AT1, AT2) for mediating changes in renal hemodynamics was studied in
anesthetized rats one month after coronary artery ligation (MI). AT1
antagonism with losartan alone decreased mean arterial pressure
(MAP), total peripheral resistance (TPR) and renal resistance (RR) in
control and MI rats to a similar extent without affecting renal blood
flow (RBF) or RBF as a percent of cardiac output (%RBF/CO). In
contrast, AT2 antagonism with PD123319 alone significantly reduced
MAP and RR in MI rats without affecting these parameters in control
rats. TPR and %RBF/CO were not changed significantly in either group.
In contrast, combined AT1 and AT2 receptor inhibition lowered TPR and
RR, and increased RBF and %RBF/CO, thus mimicking the effects of
renin or ACE inhibition in MI rats. We conclude that angiotensin II
acts at both AT1 and AT2 receptor sites in rats with reduced cardiac
mass to modulate renal hemodynamics.
Received 2 February 1996; accepted in final form 1 May 1996.
APS Manuscript Number H101-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 May 96