PMID- 11574821 OWN - NLM STAT- MEDLINE DCOM- 20011025 LR - 20131121 IS - 0022-2143 (Print) IS - 0022-2143 (Linking) VI - 138 IP - 4 DP - 2001 Oct TI - Role of nitric oxide in acidosis-induced intestinal injury in anesthetized rats. PG - 270-6 AB - We investigated the pathogenic mechanism(s) of small intestinal injury during 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 was assessed by measuring plasma concentration of nitrite/nitrate (NOx) and by evaluating inducible NO synthase (iNOS) expression in small intestinal mucosa. Intestinal injury was assessed by measuring myeloperoxidase (MPO) activity, thiobarbituric acid reactants (TBARS), and histologic scores. HCl infusion was associated with hypotension, decreased blood pH, increased plasma concentration of NOx, augmented intestinal mucosal iNOS expression, MPO activity, TBARS, and histopathologic injury scores. Pretreatment with an iNOS 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 pathogenic mechanisms of acidosis-induced small intestinal lesions involve up-regulation of NO production by increased expression of iNOS and augmentation of superoxide radicals and MPO activity. FAU - Pedoto, A AU - Pedoto A AD - Department of Anesthesiology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA. FAU - Nandi, J AU - Nandi J FAU - Oler, A AU - Oler A FAU - Camporesi, E M AU - Camporesi EM FAU - Hakim, T S AU - Hakim TS FAU - Levine, R A AU - Levine RA LA - eng PT - Journal Article PL - United States TA - J Lab Clin Med JT - The Journal of laboratory and clinical medicine JID - 0375375 RN - 0 (Nitrates) RN - 0 (Nitrites) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 142M471B3J (Carbon Dioxide) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.11.1.7 (Peroxidase) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - S88TT14065 (Oxygen) SB - IM MH - Acidosis/*complications MH - Anesthesia MH - Animals MH - Blood Pressure MH - Carbon Dioxide/blood MH - Disease Models, Animal MH - Hemodynamics MH - Hydrogen-Ion Concentration MH - Intestinal Diseases/*etiology/pathology MH - Intestinal Mucosa/enzymology MH - *Intestine, Small/enzymology/pathology MH - Kinetics MH - Lipid Peroxidation MH - Male MH - Nitrates/blood MH - Nitric Oxide/*physiology MH - Nitric Oxide Synthase/analysis/metabolism MH - Nitric Oxide Synthase Type II MH - Nitrites/blood MH - Oxygen/blood MH - Peroxidase/analysis MH - Rats MH - Rats, Sprague-Dawley MH - Thiobarbituric Acid Reactive Substances/analysis EDAT- 2001/09/28 10:00 MHDA- 2001/10/26 10:01 CRDT- 2001/09/28 10:00 PHST- 2001/09/28 10:00 [pubmed] PHST- 2001/10/26 10:01 [medline] PHST- 2001/09/28 10:00 [entrez] AID - S0022-2143(01)52202-7 [pii] AID - 10.1067/mlc.2001.118176 [doi] PST - ppublish SO - J Lab Clin Med. 2001 Oct;138(4):270-6. doi: 10.1067/mlc.2001.118176.