CAPTOPRIL INCREASES ENDOTHELIN SERUM CONCENTRATIONS AND PRESERVES INTESTINAL-MUCOSA AFTER MESENTERIC ISCHEMIA-REPERFUSION INJURY

Endothelial cells modulate the tone of the underlying smooth muscle by generating endothelium-derived relaxing and constricting factors. Cap topril (CPT), unlike other angiotensin-converting enzyme (ACE) inhibit ors, contains a sulfhydryl (-SH) group and can act as a free radical s cavenger. Iloprost (ILO) is a synthetic analogue of prostacyclin and m imics the effects of this compound. This study was designed to investi gate the effect of ILO and CPT on the mechanism of endothelin (ET) rel ease after mesenteric ischemia-reperfusion (I/R) injury in the rat. Sp rague-Dawley rats were divided into five groups: sham-operated, contro l, ILO (25 mu g/kg), CPT (10 mu g/kg), and ILO+CPT. The superior mesen teric artery was occluded for 30 min and then allowed 90 min of reperf usion, except in the sham-operated group, and the corresponding agents were given to the treated groups prior to UR injury. After I/R injury , portal venous blood was obtained for ET assay, and ileal tissue samp les were also obtained for the determination of malondialdehyde (MDA), prostaglandin E(2) (PGE(2)) and leukotriene C-4 (LTC(4)) and for hist opathological examination. MDA levels were significantly lower in the CPT, ILO and, ILO+CPT groups than in the control group, indicating the inhibition of lipid peroxidation in all groups. ET levels increased i n the control group, and this increase was reversed with ILO. In the C PT group, ET levels were significantly increased, and the addition of ILO did not affect this increase. Significant cytopreservative effect was achieved with ILO and CPT, the latter being more prominent histopa thologically. CPT exerts a significant protective effect on the intest inal mucosa after I/R injury. This protection is accomplished by incre ased ET levels and seems to be unrelated to its inhibitory effect on l ipid peroxidation and also unrelated to the arachidonic acid cascade.