Endothelin release is augmented with captopril in rat ischemia-reperfusion injury of the liver

Res Exp Med (Berl). 1996;196(4):227-33. doi: 10.1007/BF02576845.

Abstract

The reactive oxygen metabolites (ROMs) and the vascular endothelial factors such as endothelins (ETs) and thromboxane A2 (TxA2) were found to be mediators of the reperfusion component of ischemia-reperfusion (I/R) injury. Captopril (CPT), a sulfydryl (-SH) group containing angiotensin-converting enzyme inhibitor, has been shown to reverse I/R injury by its ROM scavenging effect. In this experimental study, the effects of CPT and BM 13.177 (a TxA2 receptor antagonist) were assessed on liver I/R injury in rats. Four groups of Wistar albino rats were either sham-operated, control, CPT or BM 13.177-treated. The middle and left lateral hepatic arteries and portal veins were occluded in each group but the sham and the corresponding agents were given to the animals prior to I/R injury. After I/R injury, blood was drawn from the suprahepatic inferior vena cava for ET-1-like activity assay and liver tissue samples were obtained for the determination of prostaglandin E2 (PGE2), leukotriene C4 (LTC4) and histopathologic examination. PGE2 and ET-1 levels were increased significantly in the control group compared with the sham-operated group. In the CPT group, LTC4, PGE2 and ET-1 levels were significantly increased compared with the control group, while only ET-1 levels were not different from those of the control group in the BM 13.177-treated group. It is concluded that ET-1 release increases in response to I/R injury in rat liver and CPT further increases this release. It also appears that CPT has a stimulatory effect on arachidonic acid metabolism in addition to its free radical scavenging effect.

MeSH terms

  • Animals
  • Captopril / pharmacology*
  • Dinoprostone / blood
  • Endothelin-1 / blood
  • Endothelin-1 / metabolism*
  • Free Radical Scavengers / metabolism
  • Leukotriene C4 / blood
  • Liver / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / metabolism*
  • Vasodilator Agents / pharmacology

Substances

  • Endothelin-1
  • Free Radical Scavengers
  • Reactive Oxygen Species
  • Vasodilator Agents
  • Leukotriene C4
  • Captopril
  • Dinoprostone