Abstract
Low doses of the intragastrically (i.g.) administered nitric oxide (NO) donors, 1,2,3,4-oxatriazolium,5-amino-3-(3,4-dichlorophenyl)-chloride (GEA 3162; 0.3 mg/kg) and 3-morpholino-sydnonimine (SIN-1; 1 mg/kg), inhibited gastric 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-induced gastric lesions although a clear blood pressure-lowering effect was seen. Neither the inhibition nor the exacerbation of ulceration was correlated with changes in blood pressure or prostaglandin E 2 release from the mucosal tissue. The relatively small difference between the gastroprotective and damaging doses suggests that orally administered NO donors, especially in the case of GEA 3162, may have a narrow gastric safety margin.
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