Response of cerebral blood vessels to an endogenous inhibitor of
nitric oxide synthase.
Faraci, Frank M., Johnny E. Brian, Jr, and Donald D. Heistad.
Departments of Internal Medicine, Pharmacology, and Anesthesia
Cardiovascular Center, University of Iowa College of Medicine, Iowa
City, Iowa 52242, USA
APStracts 2:0251H, 1995.
We examined effects of NG,NG-Dimethyl-L-arginine (asymmetric
dimethylarginine, ADMA), an endogenous inhibitor of nitric oxide
synthase, on cerebral vascular responses using cranial windows in
anesthetized rats and rabbits. Under control conditions in rats,
topical application of 10 and 100 uM ADMA constricted the basilar
artery by 9+/-2 (mean+/-SE) and 19+/-1% (P<0.05, n=8),
respectively, from a baseline diameter of 213+/-19 um. ADMA (10 and
100 uM) produced marked inhibition of vasodilation in response to
acetylcholine without inhibiting vasodilatation in response to
nitroprusside. ADMA (1-100 uM) inhibited activity of brain nitric
oxide synthase (measured as the conversion of [14C]L-arginine to
[14C]L-citrulline). In cerebrum and cerebellum, 50% inhibition of
activity of NO-synthase was produced by 2.3+/-0.4 and 1.8+/-0.1 uM
ADMA, respectively. In rabbits, treatment with ADMA (300 uM)
decreased baseline diameter of cerebral arterioles (control diameter
= 93+/-10 um) by 11+/-2% (P<0.05, n=10). In response to 1 uM
acetylcholine, cerebral arterioles dilated by 36+/-6 and 13+/-4%
(P<0.05 vs control) in the absence and presence of ADMA,
respectively. Effects of ADMA were prevented by L-arginine. Thus,
ADMA inhibits activity of brain NO-synthase and relaxation of
cerebral blood vessels in response to acetylcholine. Because ADMA is
produced in relatively high concentrations in brain, it may be an
important endogenous modulator of cerebral vascular tone under
resting conditions and in response to vasoactive stimuli.
Received 27 February 1995; accepted in final form 24 may 1995.
APS Manuscript Number H181-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.