Suppressed impact of nitric oxide on renal arteriolar function in
rats with chronic heart failure .
Ikenaga, Hideki, Naohito Ishii, Sean P. Didion, Kun Zhang, Kurtis G.
Cornish, Kaushik P. Patel, William G. Mayhan, and Pamela K. Carmines.
Department of Physiology and Biophysics, University of Nebraska
College of Medicine, Omaha, Nebraska 68198-4575
APStracts 5:0178F, 1998.
Experiments were performed to test the hypothesis that experimental
heart failure (HF) is associated with altered NO-dependent influences
on the renal microvasculature, including diminished modulation of
constrictor responses to ANG II. Eight-to-ten weeks after inducing HF
in rats by coronary artery ligation, enalaprilat was administered to
suppress ANG II synthesis and renal arteriolar function was studied
using the in vitro blood-perfused juxtamedullary nephron technique.
In kidneys from sham rats, NO synthase inhibition (100 (M N(-nitro
-[lambda]-arginine, [lambda]-NNA) reduced afferent arteriolar diameter
by 4.1 ( 0.6 (m and enhanced ANG II responsiveness (10 nM ANG II
decreased afferent diameter by 10.1 ( 1.4 (m before and 12.8 ( 1.6 (m
during [lambda]-NNA treatment; P < 0.05). In kidneys from HF rats,
[lambda]-NNA did not alter afferent arteriolar baseline diameter or
ANG II responsiveness (10 nM ANG II decreased diameter by 12.5 ( 1.5
(m before and 12.5 ( 2.3 (m during [lambda]-NNA). The effects of
[lambda]-NNA on efferent arteriolar function were also abated in HF
rats. In renal cortex of HF rats, NO synthase activity was decreased
by 63% and superoxide dismutase activity was diminished by 39%,
relative to tissue from sham-operated rats. Urinary nitrate/nitrite
excretion was also reduced in HF rats. Thus, both diminished
synthesis and augmented degradation likely contribute to a decreased
renal microvascular impact of endogenous NO during chronic HF, the
consequences of which include loss of NO-dependent modulation of ANG
II-induced vasoconstriction.
Received 30 January 1998; accepted in final form 1 October 1998.
APS Manuscript Number F21-8.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 20 October 1998