Integrative study on hepatic anaphylaxis

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As the first project of this research, we studied effects of anaphylaxis on hepatic vascular resistance distribution and liver weight in isolated perfused sensitized livers of guinea pigs, rats, and rabbits. In response to antigen, presinusoidal resistances increased in a greater magnitude than the postsinusoidal resistances with liver weight gain in guinea pigs, while almost selective venoconstriction of the presinusoids and liver weight loss were observed in rats and rabbits. Second, the role of shear stress in nitric oxide (NO)-mediated attenuation of anaphylactic venoconstriction was studied using an isolated ovalbumin-sensitized guinea pig liver. Hepatic anaphylaxis can increase NO production in a shear stress-independent manner, and dilates similarly both pre- and post-sinusoids, while NO produced in a shear stress-dependent manner attenuates predominantly venoconstriction of the presinusoids where shear stress is preferentially increased. Third, we determined what chemical media … More tors are involved in anaphylaxis-induced segmental venoconstriction in perfused livers isolated from ovalbumin sensitized guinea pigs. We found that anaphylaxis-induced pre-sinusoidal constriction is mainly caused by platelet-activating factor and the post-sinusoidal constriction by leukotrienes in guinea pig livers. Fourth, we determined the roles of mast cells and Kupffer cells, resident intravascular macrophages, in rat hepatic anaphylaxis. We showed that hepatic anaphylactic vasoconstriction is mediated mainly by mast cells, but not exclusively. Kupffer cells are not involved in rat hepatic anaphylactic vasoconstriction. Finally, we determined the roles of liver and splanchnic vascular bed in anaphylactic hypotension in anesthetized rats. We demonstrated that liver and splanchnic vascular beds are involved in anaphylactic hypotension presumably due to anaphylactic presinusoidal contraction-induced portal hypertension, which induced splanchnic congestion resulting in a decrease in circulating blood volume and thus systemic arterial hypotension. Less