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

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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 × 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 μM 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 μM), 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 withL-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).

Keywords: ATP; acetylcholine; hepatic artery; nitric oxide; perfused rat liver; vasodilator

Document Type: Research Article

DOI: http://dx.doi.org/10.1046/j.1365-201X.2001.00809.x

Affiliations: Academic Department of Surgery, Liver Sciences Unit, Guy’s, King’s and St Thomas’ School of Medicine, St Thomas’ Hospital, London, UK

Publication date: April 1, 2001

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