Abstract
The dual role of nitric oxide as a cytoprotective or a cytotoxic free radical gas has been noted in various types of pathophysiological conditions, including the digestive system. The aim of this study was to examine the role of nitric oxide in the mucosal injury induced by ischemia-reperfusion in the rat small intestine. A transient intestinal ischemia was produced in the catheterized ileal segments of rats by occluding the anterior mesenteric artery for 60 min. Nitric oxide metabolites (NO2− and NO3−) and lactate dehydrogenase activity in perfusates of the intestinal lumen were measured over 5 hr periods. The time-course of histological changes in small intestine was also observed. After ischemia-reperfusion, nitric oxide release in the intestinal lumen increased significantly and the dynamics of nitric oxide release correlated with that of lactate dehydrogenase leakage. The administration of NG-nitro-l-arginine methyl ester (1.0–2.5 mg/kg) inhibited this increased nitric oxide release and the lactate dehydrogenase leakage and afforded protection against the mucosal injury induced by ischemia-reperfusion. In conclusion, the nitric oxide production that was accelerated by ischemia-reperfusion of small intestine may possibly participate in the breakdown of intestinal mucosa after ischemia-reperfusion insult.
Footnotes
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Send reprint requests to: Kimihiro Yamashita, Ph.D., Department of Pharmacology, Nagasaki University School of Medicine, 1–12-4 Sakamoto, Nagasaki 852-8523, Japan.
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↵1 This work was supported in part by the Japan Research Foundation for Clinical Pharmacology and Grant-in-Aids for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.
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↵2 Current address: Kimihiro Yamashita, Faculty of Environmental Studies, Nagasaki University, 1–14 Bunkyo-machi, Nagasaki 852-8521, Japan.
- Abbreviations:
- LDH
- lactate dehydrogenase
- L-NAME
- NG-nitro-l-arginine methyl ester
- NO
- nitric oxide
- NOS
- nitric oxide synthase
- iNOS
- inducible nitric oxide synthase
- Received March 6, 1998.
- Accepted June 1, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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