title: Effects of platelet-activating factor, thromboxane A2 and leukotriene D4 on isolated perfused rat liver.
abstract: Vasoconstrictive lipid mediators, thromboxane A(2) (TxA(2)), platelet-activating factor (PAF) and leukotriene D(4) (LTD(4)) have been implicated as mediators of liver diseases. There are species differences in the primary site of hepatic vasoconstriction in response to these mediators. We determined the effects of a TxA(2) analogue (U-46619), PAF and LTD(4) on the vascular resistance distribution, weight and oxygen consumption of isolated rat livers portally perfused with blood. The sinusoidal pressure was measured by the double occlusion pressure (P(do)), and was used to determine the pre- (R(pre)) and post-sinusoidal (R(post)) resistances. All these three mediators increased the hepatic total vascular resistance (R(t)). The responsiveness to PAF was 100 times greater than that to U-46619 or LTD(4). Both of PAF and U-46619 predominantly increased R(pre) over R(post). At the comparable increased R(t) levels, U-46619 more preferentially increased R(pre) than PAF. In contrast, LTD(4) increased both the R(pre) and R(post) to similar extent. U-46619 caused liver weight loss, while high concentrations of either LTD(4) or PAF produced liver weight gain, which was caused by substantial post-sinusoidal constriction and increased P(do). PAF and U-46619 decreased hepatic oxygen consumption while LTD(4) induced biphasic change of an initial transient decrease followed by an increase. In conclusion, PAF is the most potent vasoconstrictor of rat hepatic vessels among these three mediators. Both TxA(2) and PAF constrict the pre-sinusoidal veins predominantly. TxA(2) more preferentially constricts the pre-sinusoids than PAF, resulting in liver weight loss. However LTD(4) constricts both the pre- and post-sinusoidal veins similarly. High concentrations of LTD(4) and PAF cause liver weight gain by substantial post-sinusoidal constriction. PAF and TxA(2) decrease hepatic oxygen consumption, whereas LTD(4) causes a biphasic change of it.
authors.affiliation: Department of Physiology, Kanazawa Medical University, Uchinada 920-0293, Japan.
authors.forename: Sen
authors.initials: S
authors.lastname: Cui
authors.forename: Toshishige
authors.initials: T
authors.lastname: Shibamoto
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Takano
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kurata
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D017998:Leukotriene D4 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010101:Oxygen Consumption / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D010972:Platelet Activating Factor; D013928:Thromboxane A2; D017998:Leukotriene D4; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid