Effects of nitric oxide donors GEA 3162 and SIN-1 on ethanol-induced gastric ulceration in rats

Low doses of the intragastrically (i.g.) administered nitric oxide (NO) don ors, 1,2,3,4-oxatriazolium, 5-amino-3 -(3,4-dichlorophenyl)chloride (GEA 31 62; 0.3 mg/kg) and 3-morpholino-sydnonimine (SIN-1; 1 mg/kg), inhibited gas tric ulceration induced by ethanol (94%) in anesthetized rats. In contrast, higher doses of these NO donors administered i.g. exacerbated the damage. When administered intravenously, the NO donors had no effect on ethanol-ind uced gastric lesions although a clear blood pressure-lowering effect was se en. Neither the inhibition nor the exacerbation of ulceration was correlate d with changes in blood pressure or prostaglandin E-2 release from the muco sal tissue. The relatively small difference between the gastroprotective an d damaging doses suggests that orally administered NO donors, especially in the case of GEA 3162, may have a narrow gastric safety margin. (C) 1999 El sevier Science B.V. All rights reserved.