Nitric oxide synthase inhibitors affect nitric oxide synthesis in normoxic but not in ischemic organs during intestinal ischemia and early reperfusion

Inhibition of endogenous nitric oxide (NO) synthesis during early intestinal ischemia/reperfusion (I/Ri) enhances remote organ damage related to I/Ri. However, the effects of NO synthase (NOS) inhibitors on NO formation in various organs have not yet been specified. We therefore investigated the eff...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of laboratory and clinical medicine Vol. 140; no. 5; pp. 303 - 311
Main Authors:	Kozlov, Andrey V., Sobhian, Babak, Duvigneau, Johanna C., Costantino, Guiseppina, Gemeiner, Manfred, Nohl, Hans, Redl, Heinz, Bahrami, Soheyl
Format:	Journal Article
Language:	English
Published:	Saint Louis, MO Mosby, Inc 01-11-2002 Elsevier
Subjects:	Animals Arginine - pharmacology Biological and medical sciences Disease Models, Animal Electron Spin Resonance Spectroscopy Enzyme Inhibitors - pharmacology Gastroenterology. Liver. Pancreas. Abdomen Intestines - drug effects Intestines - enzymology Liver - drug effects Liver - enzymology Lung - drug effects Lung - enzymology Male Medical sciences Nitric Oxide - biosynthesis Nitric Oxide - blood Nitric Oxide Synthase - antagonists & inhibitors Nitric Oxide Synthase - biosynthesis Nitric Oxide Synthase - genetics Nitric Oxide Synthase Type II omega-N-Methylarginine - pharmacology Other diseases. Semiology Rats Rats, Sprague-Dawley Reperfusion Injury - enzymology Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Stomach. Duodenum. Small intestine. Colon. Rectum. Anus cNOS NO EPR ecNOS mRNA DETC-Cu EDTA I/R LPS RBC RT-PCR DETC-Fe iNOS Hb SEM I/Ri Biochemical analysis Rat Enzyme Pathogenesis Rodentia Gut Enzyme inhibitor Cardiovascular disease Nitric-oxide synthase Vertebrata Experimental disease Mammalia L-aminoacid Reperfusion Arginine Ischemia Aminoacid Animal Nitric oxide Digestive diseases Intestinal disease Oxidoreductases Molecular biology Reverse transcription polymerase chain reaction
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Inhibition of endogenous nitric oxide (NO) synthesis during early intestinal ischemia/reperfusion (I/Ri) enhances remote organ damage related to I/Ri. However, the effects of NO synthase (NOS) inhibitors on NO formation in various organs have not yet been specified. We therefore investigated the effects of N-G-monomethyl-L-arginine (L-NMMA), a nonspecific NOS inhibitor, and L-arginine, the NOS substrate, on NO formed in ischemic intestine versus normoxic remote organs (lung and liver). We used electron paramagnetic resonance spectroscopy and a specific NO trap to assay NO in blood, intestine, lung, and liver of rats subjected to local I/Ri, with and without L-NMMA and L-arginine supplementation. We found that I/Ri increased NO levels in the intestine and blood, but not in the remote organs lung and liver. Administration of L-NMMA before I/Ri decreased I/Ri-independent basal NO levels in normoxic lung and liver without influencing I/Ri-induced increase in NO levels in intestinal tissue or in blood. L-arginine supplementation increased circulating levels of NO, with sensitivity to L-NMMA, without affecting NO levels in normoxic or ischemic tissue. Our data suggest that NOS activity controls the NO generated in normally perfused remote organs during early I/Ri. Hence NOS inhibitors, when administered during I/Ri, decrease physiological NO levels in normoxic remote organs without affecting increased NO levels originating from ischemic intestine. This may explain the harmful effect of nonspecific NOS inhibitors during early I/Ri. In addition, the generation of NO in remote organs is not limited by tissue L-arginine concentrations and, therefore, not influenced by exogenous L-arginine. The protective effect of L-arginine supplementation during I/Ri is probably related to increasing intravascular NO formation. (J Lab Clin Med 2002;140:303-11)
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-2143 1532-6543
DOI:	10.1067/mlc.2002.128180