Prostaglandins, Leukotrienesand Essential Fatty Acids (1998)59(6), 379-383 © 1998 HarcourtBrace & Co. Ltd Nitric oxide and endothelin relationship in intestinal ischemia/reperfusion injury (~. U. Durakbasa, ~ T. E. Dagli, ~ H. Mouni, 2 G. Haklar, 2 A. S. Bilsel, 2 M. Yuksel, 2 A. O. Aktan 3 1Department of Pediatric Surgery =Department of Biochemistry 3Department of General Surgery, Marmara University School of Medicine, ]stanbul, Turkey Summary Gastrointestinal mucosal blood flow is dependent on a balanced release of vasoactive substances from endothelium. Nitric oxide (NO) may increase the flow by vasodilatation and/or antiaggregation whereas endothelin (ET) may decrease it by vasoconstriction and aggregation. NO and ET may have counterbalancing effects on each other in tissue damage. In order to test this hypothesis, in this study on rats, L-arginine to increase NO levels and NG-nitro-L-arginine methyl esther (L-NAME) to decrease NO levels have been used in an intestinal ischemia/ reperfusion (I/R) injury model and portal vein ET response was evaluated. Lipid peroxidation product measurements and chemiluminescence (CL) studies were also carried out in ileal tissue samples. Intestinal I/R injury caused an increase in portal venous ET levels with levels of 9.4_+0.5 fmol/ml in sham operation and 14.8_+1.6 fmol/ml in I/R group. ET level of L-NAME-sh group was lower than that of sham-operated group and also ET level of L-NAME-I/R group was lower than that of I/R group. This yielded the conclusion that inhibition of NO synthesis decreases portal venous ET levels in this model. Increased NO production by L-arginine caused increased ET levels in sham operated groups but this effect was not observed in I/R injury state. This study also showed that inhibition of NO synthesis has a protective role by reducing the reperfusion damage in this model. It is likely that NO and ET have a feedback effect on each other both under physiologic conditions and I/R injury. INTRODUCTION After an ischemic insuk, reperfusion is inevitable if the organ or system in question is to survive. However, it has been shown clearly that the damage brought about by reperfusion is much bigger than ischemia itself. 1,2 The vascular endothelium is very active in regulating the vascular tonus and endothelial cell dysfunction is thought to be the 'trigger' of reperfusion injury. 3 Endo- thelial cells can produce the potent vasoconstrictor and aggregator endothelin (ET) and also the vasodilator and antiaggregator nitric oxide (NO)) '4 In different experi- mental studiest, either NO donors or NO inhibitors have been shown to be protective? -s In addition, increased Received 20 August 1998 Accepted 9 October 1998 Correspondence to: A. O. Aktan, Marmara University Hospital, Department of General Surgery, Attunizade 81190 Istanbul, Turkey. Fax: +90 216 3250323 levels of ET have been demonstrated in portal venous blood following intestinal I/R injury. 9 However, the possi- ble interaction between NO and ET in I/R injury has not been established. NO and ET may have counterbalancing effects on each other in tissue damage. In order to test this hypothesis, L-arginine to increase NO levels and NC-nitro-L-arginine methyl esther (L-NAME) to decrease NO levels have been administered in an intestinal I/R injury model on rats and ET response was evaluated. MATERIALS AND METHODS Experiments were performed on 79 female Wistar Albino rats (weighing 160-220g) initially anesthetized with urethane (1.6 mg/kg, i.p.). An intratracheal cannula was placed through a midline incision and tracheotomy to facilitate breathing. The right jugular vein was cannu- lated for infusion. Rats were randomly divided into eight 379