title: Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis.
abstract: In cirrhosis, lipopolysaccharide (LPS, a product of Gram-negative bacteria) in the blood may cause septic shock. LPS-elicited induction of arterial inducible nitric oxide synthase (iNOS) results in nitric oxide (NO)-induced vasodilation, which causes arterial hypotension and hyporeactivity to alpha(1)-adrenergic constrictors. In vitro studies have suggested that vasopressin inhibits iNOS expression in cultured vascular smooth muscle cells exposed to LPS. Thus, the aim of this study was to investigate the effects of terlipressin administration (a vasopressin analog) on in vivo LPS-induced aortic iNOS in rats with cirrhosis. LPS (1 mg/kg, intravenously) was administered followed by the intravenous administration of terlipressin (0.05 mg/kg, intravenously) or placebo 1 hour later. Arterial pressure was measured, and contractions to phenylephrine (an alpha(1)-adrenoceptor agonist), iNOS activity, and iNOS expressions (mRNA and protein) were investigated in isolated aortas. LPS-induced arterial hypotension and aortic hyporeactivity to phenylephrine were abolished in rats that received terlipressin. LPS-induced aortic iNOS activity and expression were suppressed in terlipressin-treated rats. In conclusion, in LPS-challenged rats with cirrhosis, terlipressin administration inhibits in vivo LPS-induced aortic iNOS expression. Terlipressin administration may be a novel approach for the treatment of arterial hypotension and hyporeactivity to alpha(1)-adrenergic constrictors in patients with cirrhosis and septic shock.
authors.affiliation: Laboratoire d'Hémodynamique Splanchnique et de Biologie Vasculaire, INSERM U-481, Hôpital Beaujon, Paris, France. rmoreau@bichat.inserm.fr
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.forename: Eric
authors.initials: E
authors.lastname: Barrière
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Tazi
authors.forename: Bernard
authors.initials: B
authors.lastname: Lardeux
authors.forename: Delphine
authors.initials: D
authors.lastname: Dargère
authors.forename: Waldemar
authors.initials: W
authors.lastname: Urbanowicz
authors.forename: Odile
authors.initials: O
authors.lastname: Poirel
authors.forename: Laurence
authors.initials: L
authors.lastname: Chauvelot-Moachon
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Guimont
authors.forename: Dominique
authors.initials: D
authors.lastname: Bernuau
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008070:Lipopolysaccharides; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy / Q000378:metabolism*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000077585:Terlipressin; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C090663:N(6)-(1-iminoethyl)lysine; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D008236:Lypressin; D000077585:Terlipressin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000410:Alanine Transaminase; D008239:Lysine