Role of nitric oxide in acidosis-induced intestinal injury in anesthetizedrats

We investigated the pathogenic mechanism(s) of small intestinal Injury duri ng acidosis in relation to circulating nitric oxide (NO) in an experimental rat model. Rats were anesthetized, paralyzed, and mechanically ventilated with room air. Hydrochloric acid (0.16 mmol bolus followed by 0.132 mmol/kg /h) was infused through the jugular vein for 5 hours. Control rats received a saline infusion. Arterial blood gases, blood pressure, and blood pH were measured every 30 minutes. The involvement of NO in this acidosis model wa s assessed by measuring plasma concentration of nitrite/nitrate (NOx) and b y evaluating inducible NO synthase (iNOS) expression in small intestinal mu cosa. Intestinal injury was assessed by measuring myeloperoxidase (MPO) act ivity, thiobarbituric acid reactants (TBARS), and histologic scores. HCl in fusion was associated with hypotension, decreased blood pH, increased plasm a concentration of NOx, augmented intestinal mucosal MOS expression, MPO ac tivity, TBARS, and histopathologic injury scores. Pretreatment with an MOS inhibitor, aminoguanidine (AG, 50 mg/kg), reversed HCl-induced hypotension without a change in blood pH. HCl-induced lesions, MPO activity, TBARS, and plasma NOx production were decreased by AG. Our data show that the pathoge nic mechanisms of acidosis-induced small intestinal lesions involve up-regu lation of NO production by increased expression of iNOS and augmentation of superoxide radicals and MPO activity.