title: Nitric oxide modulates acetylcholine-induced vasodilatation in the hepatic arterial vasculature of the dual-perfused rat liver.
abstract: The role of nitric oxide in the modulation of hepatic arterial vascular reactivity was investigated in an isolated dual-perfused rat liver preparation. Twelve male Wistar rats (200-250 g) were anaesthetized with sodium pentobarbitone (60 mg kg-1 i.p.). The livers were then excised and perfused in vitro through hepatic arterial and portal venous cannulae at constant flow rates. Concentration-dependent dose-response curves to acetylcholine (10(-8)-10(-5) M), sodium nitroprusside (10-6(-5) x 10(-4) M), and adenosine triphosphate (ATP) (10(-8)-10(-5) M) in the hepatic artery were constructed after the tone was raised by addition of methoxamine (3 micorM L(-1)). Acetylcholine-induced vasodilatation in the hepatic artery was significantly attenuated with inhibition of nitric oxide synthase by using NG-nitro-L-arginine methyl ester (30 microM), Emax = 51.7 +/- 2.8 vs. 32.5 +/- 3.1 mmHg, before vs. after NG-nitro-L-arginine methyl ester, respectively. ATP-induced hepatic arterial vasoconstriction which was significantly enhanced with L-NAME, Emax = 94.0 +/- 9.3 vs. 127.0 +/- 8.0 mmHg, before vs. after NG-nitro-L-arginine methyl ester, respectively. Sodium nitroprusside-induced hepatic arterial vasodilatation remained unchanged with NG-nitro-L-arginine methyl ester, Emax = 57.0 +/- 3.4 vs. 57.0 +/- 4.1, before vs. after NG-nitro-L-arginine methyl ester, respectively. The data from the present study suggest that acetylcholine-induced vasodilatation in the intrahepatic arterial vasculature of the rat liver is at least, in part, mediated by the release of nitric oxide. In addition, ATP-induced hepatic arterial vasoconstriction is also modulated by the release of nitric oxide (*P < 0.05, Student's paired t-test).
authors: Academic Department of Surgery, Liver Sciences Unit, Guy's, King's and St Thomas' School of Medicine, St Thomas' Hospital, London, UK.
authors: W
authors: W
authors: Yang
authors: I S
authors: IS
authors: Benjamin
authors: B
authors: B
authors: Alexander
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006499:Hepatic Artery / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D011169:Portal Vein / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D008729:Methoxamine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester