Effects of platelet-activating factor and thromboxane A2 on isolated perfused-guinea pig liver

Abstract Lipid mediators, thromboxane A 2 (TxA 2 ) and platelet-activating factor (PAF), are potent vasoconstrictors, and have been implicated as mediators of liver diseases, such as ischemic-reperfusion injury. We determined the effects of a TxA 2 analogue (U-46619) and PAF on the vascular resistance distribution and liver weight (wt) in isolated guinea pig livers perfused with blood via the portal vein. 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. U-46619 and PAF concentration-dependently increased the hepatic total vascular resistance ( R t ). The minimum concentration at which significant vasoconstriction occurs was 0.001 μM for PAF and 0.1 μM for U-46619. Moreover, the concentration of U-46619 required to increase R t to the same magnitude is 100 times higher than PAF. Thus, the responsiveness to PAF was greater than that to U-46619. Both agents increased predominantly R pre over R post . U-46619 caused a sustained liver weight loss. In contrast, PAF also caused liver weight loss at lower concentrations, but it produced liver weight gain at higher concentrations (2.5±0.3 per 10 g liver weight at 1 μM PAF), which was caused by substantial post-sinusoidal constriction and increased P do . In conclusion, both TxA 2 and PAF contract predominantly the pre-sinusoidal veins. TxA 2 causes liver weight loss, while PAF at high concentrations increases liver weight due to substantial post-sinusoidal constriction in isolated guinea pig livers.