In vivo treatment with endotoxin induces nitric oxide synthase in rat main pulmonary artery.
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.
Griffiths
M J
MJ
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Liu
S
S
Curzen
N P
NP
Messent
M
M
Evans
T W
TW
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D006152:Cyclic GMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D019001:Nitric Oxide Synthase; D010656:Phenylephrine / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D011189:Potassium Chloride; D011651:Pulmonary Artery / Q000201:enzymology* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine
D006146:Guanidines; D008070:Lipopolysaccharides; D010714:Phosphatidylethanolamines; D012333:RNA, Messenger; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D011189:Potassium Chloride; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; C004479:pimagedine