Effects of l-NAME on thromboxane A2-induced venoconstriction in isolated perfused livers from rat, guinea pig and mouse

Effects of l-NAME on U-46619 (a thromboxane A2, analogue) -induced hepatic segmental venoconstriction were examined in mouse, rat and guinea pig isolated perfused livers. All livers were perfused portally and recirculatingly at a constant flow with diluted blood. U-46619 was administrated into the reservoir in a cumulative manner to gain the concentrations of 0.001–3 μM at 10 min after l-NAME or d-NAME (100 μM). The portal venous pressure, hepatic venous pressure and perfusate flow were monitored. In addition, the sinusoidal pressure was measured by the double occlusion pressure, and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. U-46619 concentration-dependently caused predominant presinusoidal constriction in all three species. The rat livers were the strongest while the mouse livers were the weakest in responsiveness and sensitivity to U-46619. l-NAME mainly augmented the U-46619-induced increases in Rpre, but not in Rpost, in rat and guinea pig. This augmentation was stronger in rat. However, l-NAME did not augment the response to U-46619 in mouse. In conclusion, in rat and guinea pig, NO may be released selectively from the presinusoids in response to U-46619, and then attenuate the U-46619-induced presinusoidal constriction. In mouse, U-46619-induced venoconstriction is weak and not modulated by NO.