Intraportal nicotine infusion usion in rats decreases hepatic blood flow through endothelin-1 and both endothelin A and endothelin B receptors

Smoking has been demonstrated to aggravate liver injury. Nicotine, a major pharmacological component of tobacco smoke, affects a multitude of functions. Smoking and nicotine induce synthesis of endothelin (ET)-1. The effect of intraportal infusion of nicotine on hepatic circulation and an involvement of ET-1 and ET receptor in the action of nicotine were investigated in rats. Nicotine (0-100 mug/ kg/h) was infused into the portal vein of urethane-anesthetized rats, and changes of hepatic blood flow were evaluated. Intraportal infusion of nicotine dose-dependently decreased hepatic blood flow and increased portal pressure without any alteration of heart rate or arterial blood pressure. This action of intraportal nicotine was completely abolished by pretreatment of ET-1 antibody. Either BQ485 (ETA receptor antagonist) or BQ788 (ETB receptor antagonist) partially reversed the effect of nicotine, and combination of BQ788 and BQ485 completely abolished it. These findings suggest that nicotine inhibits hepatic circulation through ET-1, and ETA and ETB receptor. (C) 2004 Elsevier Inc. All rights reserved.