AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 3 509-L518, Copyright © 1995 by American Physiological Society
In vivo treatment with endotoxin induces nitric oxide synthase in rat main pulmonary artery
M. J. Griffiths, S. Liu, N. P. Curzen, M. Messent and T. W. Evans
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Our aim was to demonstrate increased NO activity from inducible NO synthase
(iNOS) in pulmonary arteries (PA) from rats treated with endotoxin
[lipopolysaccharide (LPS), 20 mg/kg ip]. LPS treatment diminished the
contractile response of PA to potassium chloride (KCl) and phenylephrine
(PE) and increased levels of guanosine 3',5'-cyclic monophosphate (cGMP) in
endothelium-denuded vessels. Both the NO synthase (NOS) antagonists
NG-monomethyl-L-arginine (L-NMMA; nonselective) and aminoguanidine
(selective for iNOS) enhanced PE-induced contraction in endothelium-denuded
vessels from LPS-treated rats. Furthermore, L-NMMA-induced contraction of
endothelium-denuded vessels from LPS-treated rats was stereospecifically
antagonized by L-arginine and associated with decreased cGMP levels. These
data suggest that NO is produced in increased amounts from PA smooth muscle
after LPS treatment. LPS treatment caused increased expression of mRNA for
iNOS in PA. This effect of LPS was attenuated by pretreatment with
dexamethasone, suggesting that induction of NOS in PA smooth muscle
underlies the increased NO activity associated with LPS administration.
