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) 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 E2 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.
Asmawi
M Z
MZ
Medical School, University of Tampere, Finland.
Moilanen
E
E
Annala
K
K
Rahkonen
P
P
Kankaanranta
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D014230:Triazoles / Q000627:therapeutic use*
D020030:Nitric Oxide Donors; D014230:Triazoles; D000431:Ethanol; C002385:linsidomine; C082874:GEA 3162; D008981:Molsidomine; D015232:Dinoprostone