Minor involvement of nitric oxide during chronic endotoxemia in anesthetized pigs.
To study the modifications of hepatic blood flow and hepatic function over time during endotoxemia, 10 pigs received a continuous intravenous infusion of endotoxin (Endo, 160 ng. kg(-1). h(-1)) over 18 h and 7 control (Ctrl) animals received a saline infusion. The involvement of nitric oxide (NO) in this endotoxic model was assessed by measuring plasma concentrations of NO(-)(2), NO(-)(3), and cGMP, by testing vascular reactivity to ACh, and by evaluating inducible NO synthase (NOS 2) expression in hepatic biopsies. Endotoxin induced hypotensive and normokinetic shock in association with few modifications of hepatic blood flow, and hepatic injury was observed in both groups. Endotoxin did not increase plasma concentrations of NO(-)(2), NO(-)(3), and cGMP. The ACh-dependent decrease of mean arterial pressure was reduced in Endo pigs, whereas a minor difference was observed between Ctrl and Endo pigs for ACh-dependent modification of hepatic perfusion. Hepatic NOS 2 mRNA was not detected in Ctrl pigs. In Endo pigs, NOS 2 protein expression was detected only in tissues surrounding the portal vein and the inferior vena cava, whereas NOS 2 mRNA was expressed in all hepatic biopsies. Thus, although endotoxemia induces NOS 2 expression in the liver, our findings show that NO involvement is lower in pigs than in rodents during endotoxemia.
Pastor
C M
CM
Division d'Hépatologie et de Gastroentérologie, Hôpital Cantonal Universitaire de Genève, CH 1211 Geneva, Switzerland. Catherine.Pastor@medecine.unige.ch
Hadengue
A
A
Nussler
A K
AK
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D019446:Endotoxemia / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013552:Swine; D013556:Swine, Miniature; D014665:Vasodilator Agents / Q000494:pharmacology
D012333:RNA, Messenger; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D000109:Acetylcholine