The roles of platelet-activating factor and endothelin-1 in renal damage after total hepatic ischemia and reperfusion

Background. This study was designed to verify the involvement of platelet-a ctivating factor (PAF) in renal damage associated with hepatic ischemia and reperfusion (HIR) injury through the release of endothelin (ET)-1 and to d etermine the modulating effect of a specific PAF receptor antagonist on the se insults in rats, Methods. Male rats pretreated with either normal saline as a vehicle (NS gr oup) or intravenous TCV-309, a PAF receptor antagonist (TCV group), were su bjected to 120 min of total hepatic ischemia under an extracorporeal portos ystemic shunt. Plasma aspartate transaminase, creatinine, blood urea nitrog en, and ET-1 levels and the relative renal wet weight were determined under nonischemic conditions and at 1, 3, and 6 hr of reperfusion after hepatic ischemia, Changes in mean arterial blood pressure and renal tissue blood fl ow measurements in the kidney were determined throughout the experiment. Results, Increased plasma aspartate transaminase, creatinine, blood urea ni trogen, and ET-1 levels and the relative renal wet weight after HIR in the NS group were significantly suppressed by TCV-309 pretreatment. Mean arteri al blood pressure and renal tissue blood flow after HIR in the TCV group we re significantly improved when compared with those in the NS group, These e ffects resulted in attenuation of structural hepatic and renal damage with the improvement of 7-day survival (62%). Conclusions. The present study demonstrates that renal damage as well as cr itical liver injury is produced after repel fusion following 120 min of tot al hepatic ischemia, A PAF receptor antagonist may be therapeutically usefu l to protect against these types of damage via indirect modulation of plasm a ET-1 levels.