Intestinal nitric oxide in the normal and endotoxemic pig.
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.
Malmström
Rickard E
RE
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Björne
Håkan
H
Oldner
Anders
A
Wanecek
Mikael
M
Fredriksson
Marie
M
Lundberg
Jon O N
JO
Weitzberg
Eddie
E
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
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