薬理と治療

Abstract

Purpose In order to explore whether the portal venous pressure（PVP）increases in response to administration of tolvaptan or not, we determined the effect of tolvaptan, the vasopressin V2 receptor antagonist, on PVP in in vivo anesthetized Sprague-Dawley rats with and without portal hypertension induced by bile duct ligation（BDL）, and in ex vivo isolated blood-perfused rat livers. Methods In perfused livers（n＝10）, with measurement of PVP, hepatic venous pressure（HVP）,and portal venous blood flow（Qpv）, the hepatic vascular resistance（Rt（: PVP-HVP）╱Qpv）was determined. In anesthetized intact rats（n＝5）, the mean arterial blood pressure（MAP）, PVP, and mean portal venous blood flow（PBF）were measured, and the splanchnic vascular resistance （Rspl（; MAP-PVP）╱PBF）was determined. In bile duct ligated rats（n＝4）, MAP and PVP were measured. Results In perfused livers, PVP and Rt were not significantly changed from the baseline of 7.1±0.2 cmH2O and 0.19±0.003 cmH2O・mL-1・min, respectively, after consecutive injections of tolvaptan at 0.001-1μM. Subsequent injections of norepinephrine at 0.001-1μM caused no significant differences in the induced increases in PVP or Rt between tolvaptan- and vehicle-treated livers, suggesting no effects of tolvaptan on the reactivity of the portal vessels to norepinephrine. An intravenous injections of tolvaptan at 0.1, 0.3 and 1 mg╱kg into anesthetized intact or bile duct ligated rats, the basal PVP levels of which were 12.6±1.1 mmHg, did not produce any significant changes in PVP or Rspl. Conclusion Tolvaptan does not affect portal venous pressure in anesthetized rats with or without portal hypertension induced by BDL, or in isolated perfused rat livers.