Nitric oxide protects the intestine from the damage induced by laparotomy and gut manipulation

Background. The intestine is highly susceptible to free radical-induced dam age, and our earlier work. has shown that surgical stress induces the gener ation of oxygen free radicals in enterocytes, resulting in intestinal damag e along with ultrastructural changes. Since nitric oxide (NO) is an importa nt mediator of gastrointestinal function, this study looked at the effect o f NO on surgical stress-induced intestinal alterations, Materials and metho ds. Control rats and rats pretreated with the NO donor L-arginine were subj ected to surgical stress by opening the abdominal wall and handling the int estine as done during laparotomy. Enterocytes were isolated and homogenate prepared, and the protection offered by L-arginine against damage due to su rgical stress was determined and compared with normal controls. Protection to structural as well as functional aspects of the intestine was also exami ned. Results. Intestinal manipulation affected intestinal structure as asse ssed by electron microscopy. Functional impairment of the enterocyte was al so evident, with increased xanthine oxidase activity resulting in productio n of superoxide anion. This impairment is more dramatic in the crypt cells. Increased protease activity was also seen following laparotomy and handlin g. Pretreatment with the NO synthase substrate L-arginine prevented these d amaging effects. Arginine protection was abolished in the presence of the N O synthase inhibitor NG-nitro-L-arginine methyl ester, indicating the role of NO. Conclusion. Stress in the small intestine due to any surgery can aff ect enterocyte structure and function. These damaging effects can be preven ted by NO, an important modulator of cellular function. (C) 2001 Academic P ress.