Role of ang ii in hypertension produced by chronic inhibition of
nitric oxide synthase in conscious rats.
Melaragno, Matthew G., and Gregory D. Fink.
Department of Pharmacology and Toxicology, Michigan State
University, East Lansing, MI 48824-1317
APStracts 3:0002H, 1996.
These experiments tested the hypothesis that hypertension caused by
chronic inhibition of nitric oxide synthase (NOS) is associated with
augmented pressor responsiveness to ANG II. Antagonism of ANG II-AT1
receptors with losartan caused a greater fall in blood pressure (BP)
in rats treated for two weeks with the NOS inhibitor N -nitro-L
-arginine methyl ester (L-NAME) than in normotensive rats. The delayed
time course of the decline in BP implicated the slow pressor effect
(SPE) of ANG II in L-NAME hypertension. Further experiments showed
that direct elicitation of the SPE by continuous low dose (4 ng/min)
intravenous infusion of ANG II in enalapril-treated rats resulted in
a larger chronic increase in BP if NOS was inhibited. However, L-NAME
alone also caused a significant increase in BP in enalapril-treated
rats. The combined effect on BP of ANG II and L-NAME was merely
additive. These results confirm that ANG II is involved in L-NAME
hypertension. However, chronic pressor responsiveness to the peptide
is not augmented by L-NAME.
Received 23 October 1995; accepted in final form 13 December
1995.
APS Manuscript Number H993-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96