Nitric oxide donating compounds inhibit HCl-induced gastric mucosal lesions mainly via prostaglandin

Prostaglandin (PG) and nitric oxide (NO) have been known to inhibit the les ion formation induced by necrotic agents. However, no clear correlation bet ween PG and NO has been shown in the gastroprotective action against necrot ic agent-induced gastric mucosal lesions in rats. Thus, the present study w as performed to clarify this correlation. Gastric mucosal lesions were indu ced by the oral administration of 0.6 M HCl in rats. 16,16-Dimethyl PGE(2) (0.3 - 3 mug/kg, p.o.; dim-PGE(2)), sodium nitrite (0.3 and 1 mg/kg, s.c.) and sodium nitroprusside (30 and 100 mug/kg, i.v.; SNP) dose-dependently in hibited the lesion formation. Orally administered sodium nitrite or SNP (3 mg/kg) also significantly inhibited the lesion formation. The gastroprotect ive action by dim-PGE(2) was not affected by the pre-treatment with N-G-nit ro-L-arginine methylester (10 mg/kg, i.v.). The gastroprotective effect by sodium nitrite or SNP was markedly attenuated by the pre-treatment with ind omethacin(10 mg/kg, s.c.). These findings suggest that NO donating compound s inhibit the HCl-induced mucosal lesions mainly through prostaglandin, but dim-PGE(2) directly inhibits the lesions without involvement of NO in rats .