Nitric oxide prevents intestinal mitochondrial dysfunction induced by surgical stress

Background: The intestine is highly susceptible to free radical-induced dam age and earlier work has shown that surgical stress induces generation of o xygen free radicals in enterocytes, resulting in intestinal damage along wi th changes in mitochondrial structure and function. Nitric oxide is an impo rtant mediator of gastrointestinal function and this study looked at the ef fect of nitric oxide on surgical stress-induced intestinal mitochondrial al terations. Methods: Controls and rats pretreated with the nitric oxide donor L-arginin e were subjected to surgical stress by opening the abdominal wall and handl ing the intestine. Enterocytes were isolated, mitochondria prepared and the protection offered by L-arginine against damage due to surgical stress was determined. Protection to structural as well as functional aspects of mito chondria was examined. Results: Mild handling of the intestine affected the enterocyte mitochondri al structure as assessed by lipid composition and electron microscopy. Mito chondria were also functionally impaired with altered calcium flux and decr eased respiratory control ratio. Pretreatment with the nitric oxide synthas e substrate L-arginine prevented these damaging effects of surgical stress. Protection with arginine was abolished by the nitric oxide synthase inhibi tor N-G-nitro-L-arginine methyl ester, indicating the role of nitric oxide. Conclusion: Surgical stress in the small intestine can affect enterocyte mi tochondrial structure and function. These damaging effects can be prevented by nitric oxide, an important modulator of cellular function.