doi: 10.1111/j.1472-8206.2005.00365.x SHORT COMMUNICATION L-Arginine and melatonin interaction in rat intestinal ischemia–reperfusion S. Oktay Arslan a *, Ethem Gelir b , Hale Sayan b , V. Haktan Ozacmak b Departments of a Pharmacology and b Physiology, Medical School, Zonguldak Karaelmas University, Zonguldak 67600, Turkey INTRODUCTION Intestinal ischemia–reperfusion (I/R) is associated with various pathological conditions and surgical procedures. These conditions and procedures can cause disruption of intestinal barrier, impairment of gut motility and an increase in intestinal permeability. Data suggest that vascular integrity and intestinal barrier function are severely damaged due to reduced endothelial nitric oxide synthase (eNOS) activity. Apparently, reduced eNOS activity leads to decrease in nitric oxide (NO) production. Reactive oxygen species (ROS), produced during I/R, can damage cell membrane and subcellular structures, and lead to cell death and necrosis. Thus, therapeutic strategies to prevent I/R injury are focusing on antioxid- ant treatment and NO supplementation [1,2]. The present study aims to test whether the combination of melatonin which is a strong antioxidant and L-arginine which is an NO precursor is more effective or not in prevention of I/R injury. MATERIALS AND METHODS Male Wistar albino rats (230–250 g) obtained from the Zonguldak Karaelmas University Animal Care Unit were housed under standard conditions and had free access to chow and water. All procedures described here had prior approval from the local animal ethics committee of University. The animals were fasted overnight but allowed ad libitum access to water 1 day before surgical procedures. In order to make mesenteric ischemia, a midline incision was made into the peritoneal cavity under sodium thiopental (60 mg/kg) anesthesia. The small bowel was exteriorized gently to the left onto moist gauze; then, the superior mesenteric artery (SMA) was carefully isolated and ligated by using 3.0 silk suture. Afterwards, the intestines were returned to the abdomen, which was then closed with two small clamps. After 30 min of occlusion, the ligation was gently released and the intestine inspected for proper reperfusion. During all these procedures, the animal was positioned under a heating lamp in order to prevent heat loss. These surgical procedures have been carried out on six different experi- mental groups each including six animals: (1) Sham- operated control group: the rats underwent laparatomy without the occlusion of SMA and sterile saline was injected to the animals; (2) I/R group: the SMA was occluded for 30 min followed 3 h of reperfusion period; (3) I/R + L-arginine-treated group; (4) I/R + melatonin- treated group; (5) I/R + L-arginine + melatonin-treated Keywords contractile activity, interaction, ischemia and reperfusion, L-arginine, melatonin Received 11 March 2005; revised 9 May 2005; accepted 13 June 2005 *Correspondence and reprints: arslanoktay@yahoo.com ABSTRACT We investigated the combinative effects of L-arginine and melatonin on the contractile responses of terminal ileum after the intestinal ischemia–reperfusion (I/R), in vivo. Male rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (180 min). We have observed a dramatic decrease in spontaneous basal activity and Ach-induced contractile response. Our data clearly showed that the contractility decrease was ameliorated by L-arginine but not by L-NAME. Melatonin has reversed the inhibition of contractility caused by I/R injury in part. We did not observe an augmentation in the contractility of ileum when we use melatonin and L-arginine in combination, in fact, melatonin decreased the protective effect of L-arginine in intestinal I/R injury. Ó 2005 Blackwell Publishing Fundamental & Clinical Pharmacology 19 (2005) 533–535 533