Nitric oxide modulates acetylcholine-induced vasodilatation in the hepaticarterial vasculature of the dual-perfused rat liver

The role of nitric oxide in the modulation of hepatic arterial vascular rea ctivity was investigated in an isolated dual-perfused rat liver preparation . Twelve male Wistar rats (200-250 g) were anaesthetized with sodium pentob arbitone (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 trip hosphate (ATP) (10(-8)-10(-5) M) in the hepatic artery were constructed aft er the tone was raised by addition of methoxamine (3 muM L-1). Acetylcholin e-induced vasodilatation in the hepatic artery was significantly attenuated with inhibition of nitric oxide synthase by using N-G-nitro-L-arginine met hyl ester (30 muM), E-max = 51.7 +/- 2.8 vs. 32.5 +/- 3.1 mmHg, before vs. after N-G-nitro-L-arginine methyl ester, respectively. ATP-induced hepatic arterial vasoconstriction which was significantly enhanced with L-NAME, E-m ax = 94.0 +/- 9.3 vs. 127.0 +/- 8.0 mmHg, before vs. after N-G-nitro-L-argi nine methyl ester, respectively. Sodium nitroprusside-induced hepatic arter ial vasodilatation remained unchanged with N-G-nitro-L-arginine methyl este r, E-max = 57.0 +/- 3.4 vs. 57.0 +/- 4.1, before vs, after N-G-nitro-L-argi nine methyl ester, respectively. The data from the present study suggest th at acetylcholine-induced vasodilatation in the intrahepatic arterial vascul ature of the rat liver is at least. in part, mediated by the release of nit ric oxide, in addition, ATP-induced hepatic arterial vasoconstriction is al so modulated by the release of nitric oxide (*P < 0.05, Student's paired t- test).