The endothelial and non-endothelial mechanism responsible for attenuated vasoconstriction in cirrhotic rats.
The pathogenesis of the vasodilatation associated with liver cirrhosis is not fully understood, but it has recently been postulated that it may be related to an increase in nitric oxide production. The aim of this study was to compare the response of isolated aortic rings from normal and cirrhotic rats to two vasoconstrictors, phenylephrine and U46619, a thromboxane analogue. Biliary cirrhosis was induced by ligation of the common bile duct; a sham operation was performed in control animals. Five weeks later, the aorta was removed and dissected into rings for study in organ chambers. Concentration-response curves were obtained for the two vasoconstrictors from rings with intact endothelium and from rings denuded of endothelium. We found that the vasoconstriction produced by phenylephrine was decreased in cirrhotic vessels both with and without endothelium, but the response to U46619 was not modified by cirrhosis. Concentration-response curves for phenylephrine were also obtained from rings in which the synthesis of nitric oxide and prostaglandins was inhibited by NG-monomethyl-L-arginine and indomethacin, respectively. Nitric oxide synthase inhibition restored normal contractility of the rings with and without endothelium. This beneficial effect was not observed when cyclo-oxygenase activity was blocked with indomethacin. This study suggests that cirrhotic vessels are hyporeactive to vasoconstrictors and that this effect is mediated through increased nitric oxide production. The improvement observed after inhibition of the nitric oxide pathway in denuded rings led us to suggest that cirrhosis also induces nitric oxide synthase in smooth muscle cells, as previously observed by others in septic animals.
Van Obbergh
L
L
Department of Anaesthesiology, Notre Dame Hospital, University of Montreal, Canada.
Leonard
V
V
Chen
H
H
Xu
D
D
Blaise
G
G
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase