Lipopolysaccharide down-regulates inducible nitric oxide synthase expression in swine heart in vivo.
Studies of the regulation of iNOS expression have provided many contradictory results. Comparing iNOS expression profile between cell types or organs of the same animal under the same experimental conditions may provide an explanation for these conflicting results. We have examined iNOS mRNA and protein expression in heart and liver of the same group of pigs. We found that there is a sharp difference in iNOS expression between heart and liver. The iNOS mRNA and protein was constitutively expressed in the heart at high level, but was not detectable in the liver of the same control animal. Lipopolysaccharide (LPS, 100 microg/kg, i.v.) caused a marked iNOS induction in the liver, but significantly down-regulated iNOS expression in the heart. This differential iNOS expression appears to be physiologically relevant, since LPS and the iNOS inhibitor, S-methylisothiourea, exerted different effects on hepatic and myocardial blood flow. Our data demonstrate a fundamental difference in iNOS regulation in the heart and liver of swine, and may explain the contradictory data on the regulation of iNOS expression.
Cohen
Rubin I
RI
Department of Medicine, Long Island Jewish Medical Center, The Albert Einstein College of Medicine, New Hyde Park, NY 11040-1433, USA.
Hassell
Anne Marie
AM
Ye
Xiaobing
X
Marzouk
Kamel
K
Liu
Shu Fang
SF
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply / Q000201:enzymology; D008102:Liver Circulation / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007550:Isothiuronium; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C027744:S-methylisothiopseudouronium