Effects of platelet-activating factor and thromboxane A2 on isolated perfused guinea pig liver
Effects of platelet-activating factor and thromboxane A2 on isolated perfused guinea pig liver
复制标题
DOI：
10.1016/j.prpostaglandins.2003.11.002
复制
发表时间：
2004-01-01
影响因子：
2.9
通讯作者：
Kubo, K
中科院分区：
文献类型：
--
作者：
Ruan, ZH;Shibamoto, T;Kubo, K
脂质介质血栓素A(2) （TxA(2)）和血小板活化因子（PAF）是有效的血管收缩剂，被认为是肝脏疾病的介质，如缺血-再灌注损伤。我们测定了TxA2类似物（U-46619）和PAF对经门静脉灌注血液的离体豚鼠肝脏血管阻力分布和肝脏重量（wt）的影响。用双闭塞压（P-do）测量正弦波压力，并测定正弦波前（R-pre）和正弦波后（R-post）阻力。U-46619和PAF浓度依赖性地增加肝脏总血管阻力（R,）。PAF和U-46619发生显著血管收缩的最小浓度分别为0.001 muM和0.1 muM。将R-t提高到相同量级所需的U-46619浓度比PAR高100倍，因此对PAF的响应性大于对U-46619的响应性。两种药物均显著增加R-pre而非R-post。U-46619导致肝脏体重持续下降。相比之下，PAF在较低浓度下也引起肝脏重量下降，但在较高浓度下（1 muM PAF时每10g肝脏重量2.5 +/- 0.3）引起肝脏重量增加，这是由大量的正弦后收缩和P-do增加引起的。总之，TxA2和PAF主要收缩前窦静脉。TxA(2)导致肝脏重量减轻，而高浓度PAF由于离体豚鼠肝脏的大量窦后收缩而增加肝脏重量。(C) 2004爱思唯尔公司版权所有。
Lipid mediators, thromboxane A(2) (TxA(2)) and platelet-activating factor (PAF), are potent vaso-constrictors, and have been implicated as mediators of liver diseases, such as ischemic-reperfusion injury. We determined the effects of a TxA2 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,). The minimum concentration at which significant vasoconstriction occurs was 0.001 muM for PAF and 0.1 muM for U-46619. Moreover, the concentration of U-46619 required to increase R-t to the same magnitude is 100 times higher than PAR 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 10g liver weight at 1 muM PAF), which was caused by substantial post-sinusoidal constriction and increased P-do. In conclusion, both TxA2 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. (C) 2004 Elsevier Inc. All rights reserved.