Anaphylactic hepatic venoconstriction is attenuated by nitric oxide released via shear stress-dependent and -independent mechanisms in Guinea pig.

1. The role of shear stress in nitric oxide (NO)-mediated attenuation of anaphylactic venoconstriction was studied using an isolated ovalbumin-sensitized guinea pig liver. 2. Guinea pigs were actively sensitized by a subcutaneous injection of 1 mg ovalbumin. Two weeks after sensitization, the livers were perfused with diluted blood under constant flow or constant perfusion pressure. The constant flow could result in increased shear stress during constriction, while the constant perfusion pressure could prevent changes in shear stress. Using the double occlusion technique to estimate the hepatic sinusoidal pressure, pre- and postsinusoidal constriction was evaluated. Hepatic anaphylaxis was induced by an injection of ovalbumin (4 microg) into the perfusate, the volume of which was 40 mL. 3. Under either constant flow or pressure, anaphylaxis caused venoconstriction of predominantly presinusoids over postsinusoids, although anaphylactic venoconstriction under constant pressure was significantly greater than that under constant flow. When shear stress was held constant by maintaining constant perfusion pressure, a NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 100 micromol/L), potentiated similarly both pre- and postsinusoidal constriction induced by anaphylaxis. This suggests that hepatic anaphylaxis shear stress-independently generates NO, resulting in dilatation of both pre- and postsinusoidal vessels in a similar magnitude. In contrast, when shear stress was allowed to rise under constant flow, anaphylactic presinusoidal constriction was preferentially potentiated by L-NAME. 4. Hepatic anaphylaxis can increase NO production in a shear stress-independent manner and dilates similarly both pre- and postsinusoids, while NO produced in a shear stress-dependent manner attenuates predominantly venoconstriction of the presinusoids where shear stress is preferentially increased.