The action of nitric oxide on hepatic haemodynamics during secondary biliary cirrhosis in the rat.
The role of nitric oxide (NO) in portal hypertension is poorly understood. The role of NO upon hepatic arterial and portal venous vasoconstrictor responses to noradrenaline and ATP in rats with secondary biliary cirrhosis was evaluated. Cirrhosis was induced by bile duct ligation after which livers were excised and dual-perfused in vitro. Concentration-dependent dose-response curves were then constructed to hepatic arterial and portal venous noradrenaline and ATP. Hepatic arterial responses to noradrenaline and ATP were significantly attenuated in cirrhotic rats. 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME) restored attenuated hepatic arterial responses to noradrenaline and ATP in cirrhotic rats. Portal venous responses to noradrenaline in cirrhotic rats were significantly increased compared to controls and were not affected by L-NAME. However, portal venous responses to ATP were significantly attenuated in cirrhotic rats and were also not restored by L-NAME. Hepatic arterial or portal venous responses to noradrenaline did not change after infusion of L-NAME. Hepatic arterial responses to noradrenaline and ATP were significantly attenuated in cirrhotic rats, possibly due to increased production of NO. However, portal venous responses in cirrhotic rats were increased to noradrenaline and attenuated to ATP, and were not related to increased NO production.
Yang
Wenxuan
W
Liver Sciences Unit, Academic Department of Surgery, Guys, King's and St. Thomas' School of Medicine and Dentistry, St. Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK.
Benjamin
Irving S
IS
Moore
Kevin
K
Portmann
Bernard
B
Alexander
Barry
B
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006499:Hepatic Artery / Q000187:drug effects / Q000503:physiopathology; D006975:Hypertension, Portal / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000098:blood supply*; D008105:Liver Cirrhosis, Biliary / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011169:Portal Vein / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine