title: Intestinal nitric oxide in the normal and endotoxemic pig.
abstract: The gut is considered a central organ in the pathogenesis of sepsis and multiple organ failure, where several mediators, including endothelin (ET) and nitric oxide (NO), are involved. The aim of the current study was to characterize, by direct measurements, the intestinal NO production in the anesthetized pig during normal and endotoxemic conditions. In pigs subjected to endotoxin infusion, there was a progressive decrease in jejunal luminal NO levels, as well as portal venous blood flow and blood pressure. The ET- blocker 4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2'-bipyrimidin-4-yl]-benzenesulfonamide (bosentan) completely reversed the reduction in portal venous blood flow without affecting intestinal NO levels. In control pigs, the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester dose-dependently decreased intestinal NO levels and mesenteric blood flow--effects that were reversed by L-arginine. We conclude that intestinal NO is a product of mucosal NO synthase activity, and is profoundly decreased during endotoxemia in the pig.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Rickard E
authors.initials: RE
authors.lastname: Malmström
authors.forename: Håkan
authors.initials: H
authors.lastname: Björne
authors.forename: Anders
authors.initials: A
authors.lastname: Oldner
authors.forename: Mikael
authors.initials: M
authors.lastname: Wanecek
authors.forename: Marie
authors.initials: M
authors.lastname: Fredriksson
authors.forename: Jon O N
authors.initials: JO
authors.lastname: Lundberg
authors.forename: Eddie
authors.initials: E
authors.lastname: Weitzberg
mesh_terms: D000818:Animals; D019446:Endotoxemia / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D012007:Rectum / Q000187:drug effects / Q000378:metabolism; D013152:Splanchnic Circulation / Q000187:drug effects; D034421:Sus scrofa
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019331:NG-Nitroarginine Methyl Ester