DOES PGE(2) ACT AS A MEDIATOR FOR ENDOTHELIN RELEASE

To investigate the effect of iloprost (ZK 36374) and thromboxane synth etase inhibitor UK 38485 on endothelin release by the intestinal vascu lar endothelium after ischemia/reperfusion (IR) injury, five experimen tal groups were formed. The groups consisted of sham, control, ilopros t treated (ILO), UK 38485 treated (TSI), and iloprost + UK 38485 treat ed (ILO + TSI) groups. The last three groups received the correspondin g agents and then the superior mesenteric artery was clamped for 30 mi n followed by 90 min reperfusion. Endothelin levels in the portal bloo d and malondialdehyde (MDA), prostaglandin E(2) (PGE(2)) and leukotrie ne C-4 (LTC(4)) levels in the intestinal tissue were determined. The M DA levels increased significantly in the control group and this increa se was reversed in ILO, TSI, and ILO + TSI groups, the two drugs toget her showing a synergistic effect in preventing lipid peroxidation. The changes in the LTC, levels were not significant among the groups. The increased endothelin levels in the control group were reversed in ILO and TSI groups but these two agents did not have a synergistic effect . Increased PGE, levels were reversed with iloprost but neither UK 384 85 nor the combination of the two agents was effective in decreasing P GE, levels. It is concluded that endothelin release after mesenteric I R injury is relatively unrelated to lipid peroxidation and the lipoxyg enase pathway. The cyclooxygenase pathway has a direct effect on endot helin release and PGE, may act as a mediator.