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.