Nitric oxide in gastroprotection by sucralfate, mild irritant, and nocloprost. Role of mucosal blood flow.
Pretreatment with sucralfate is known to protect gastric mucosa against the damaging effect of strong irritants, and this protection is accompanied by an increase in mucosal blood flow but the mechanisms underlying these effects have not been elucidated. Similar gastroprotective and hyperemic effects can be obtained with exogenous prostaglandins (PG), mild irritants such as dilute ethanol, and by capsaicin. In this study we investigated the role of nitric oxide (NO) in the prevention of ethanol-induced gastric damage and gastric blood flow by sucralfate, mild irritant such as 20% ethanol, capsaicin, and nocloprost, a stable PGE2 analog. Pretreatment with NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase, enhanced ethanol-induced mucosal damage and reduced dose-dependently the gastroprotective and hyperemic effects of sucralfate, dilute ethanol, and capsaicin. The doses of L-NNA attenuating significantly the protective effects of sucralfate or 20% ethanol were 25-50 mg/kg, while those reducing the protection by capsaicin were 6.2-12.5 mg/kg. The attenuating effect of L-NNA on gastroprotection was reversed by L-arginine but not D-arginine. For comparison, the gastroprotective (but not hyperemic) effect of nocloprost was not affected by the pretreatment with L-NNA and/or arginine. We conclude that sucralfate, mild irritant, and capsaicin activate the NO system that may contribute to their gastroprotective effect through enhancing mucosal circulation but that NO is not essential for the mucosal protection by PGE2 analog.
Konturek
S J
SJ
Institute of Physiology, University Medical School, Krakow, Poland.
Brzozowski
T
T
Majka
J
J
Szlachcic
A
A
Czarnobilski
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects*; D007509:Irritants / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013392:Sucralfate / Q000494:pharmacology*
D007509:Irritants; D011461:Prostaglandins F, Synthetic; D019335:Nitroarginine; D009569:Nitric Oxide; D000431:Ethanol; D013392:Sucralfate; C048895:nocloprost; D001120:Arginine; D002211:Capsaicin