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 lesion formation induced by necrotic agents. However, no clear correlation between PG and NO has been shown in the gastroprotective action against necrotic agent-induced gastric mucosal lesions in rats. Thus, the present study was performed to clarify this correlation. Gastric mucosal lesions were induced by the oral administration of 0.6 M HCl in rats. 16,16-Dimethyl PGE2 (0.3-3 microg/kg, p.o.; dim-PGE2), sodium nitrite (0.3 and 1 mg/kg, s.c.) and sodium nitroprusside (30 and 100 microg/kg, i.v.; SNP) dose-dependently inhibited the lesion formation. Orally administered sodium nitrite or SNP (3 mg/kg) also significantly inhibited the lesion formation. The gastroprotective action by dim-PGE2 was not affected by the pre-treatment with N(G)-nitro-L-arginine methylester (10 mg/kg, i.v.). The gastroprotective effect by sodium nitrite or SNP was markedly attenuated by the pre-treatment with indomethacin (10 mg/kg, s.c.). These findings suggest that NO donating compounds inhibit the HCl-induced mucosal lesions mainly through prostaglandin, but dim-PGE2 directly inhibits the lesions without involvement of NO in rats.
Uchida
M
M
Food Functionality Research Institute, Meiji Milk Products Co., Ltd., Naruda, Odawara, Japan. masayuki_uchida@meiji-milk.com
Matsueda
K
K
Shoda
R
R
Muraoka
A
A
Yamato
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012977:Sodium Nitrite / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000378:metabolism / Q000517:prevention & control*
D020030:Nitric Oxide Donors; D009599:Nitroprusside; D012977:Sodium Nitrite; D015064:16,16-Dimethylprostaglandin E2; D006851:Hydrochloric Acid; D007213:Indomethacin