Exogenous nitric oxide inhibits basal no release from vascular
endothelium in vitro and in vivo.
Irenbaum;, Jakob Vinten-Johansen.
Division of Emergency Medicine, Department of Surgery, Jefferson
Medical College, Thomas Jefferson University, Philadelphia, PA 19107
-5004
APStracts 3:0235H, 1996.
This study tested the hypothesis that exogenous nitric oxide (NO)
inhibits basal release of NO in isolated rat aortic rings, and in
vivo. Thoracic aortic rings were suspended in organ chambers with
Krebs-Henseleit solution. In untreated rings, the NO-synthase
inhibitor L-NAME markedly increased basal vascular tone by 34.6+/
-5.2% of maximal force produced by 100 nM thromboxane A2-mimetic U
-46619, indicating a basal release of NO. Other rings were pretreated
with the exogenous NO-donor S-nitroso-N-acetylpenicillamine (SNAP)
for 20 minutes and then washed free of drug. In these rings, L-NAME
-induced vasoconstriction was significantly attenuated in a
concentration-dependent manner (from 34.6+/-5.2% to 25.7+/-2.9% at
SNAP=0.5 [mu]M, 15.2+/-3.1% at 1 [mu]M, and 11.9+/-2.5% at 5 [mu]M),
while having no effect on NO-independent phenylephrine-induced
vasoconstriction (35.4+/-4.7% untreated vs. 41.3+/-4.3% SNAP
pretreated, NS). In addition, the non-nitrosylated parent molecule of
SNAP, acetylpenicillamine, had no effect on the vasoconstriction
induced by L-NAME. In the In vivo studies in anesthetized rats, L
-NAME caused significant hypertensive responses (34+/-4 mmHg increase
in MABP). Subvasoactive doses of SNAP attenuated these hypertensive
responses in a dose-dependent manner (20 +/-3 mmHg increase with 10
[mu]g/kg SNAP pre-treatment and 16+/-4 mmHg increase with 20 [mu]g/kg
SNAP pre-treatment) but any dose of acetylpenicillamine studied had
no effect. Co-administration of superoxide dismutase and SNAP
significantly potentiated the inhibitory effect of the NO-donor on
vasocontraction responses to L-NAME. Furthermore, SNAP did not
attenuate the hypertensive responses to phenylephrine. These results
indicate that exogenous NO significantly inhibits basal NO release
both in vitro and in vivo, suggesting that NO plays an important
negative feedback regulatory role under physiological conditions.
Received 12 July 1995; accepted in final form 20 May 1996.
APS Manuscript Number H645-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96