Role of nitric oxide and prostaglandins in sucralfate-induced gastroprotection.
We investigated the role of nitric oxide (NO) and prostaglandins (PG) in the prevention by sucralfate of ethanol-induced gastric damage and the decrease of gastric blood flow and compared them with those obtained with nocloprost, a potent locally acting gastroprotective agent. Sucralfate and nocloprost given intragastrically (i.g.) protected dose dependently the gastric mucosa against the damage by absolute ethanol and prevented the decrease in blood flow induced by ethanol. Pretreatment with NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase decreased dose dependently the protection and the maintenance of blood flow provided by sucralfate but not by nocloprost. This decrease of sucralfate protection was antagonized by L-arginine but not D-arginine. Pretreatment with indomethacin also reversed, in part, the protective and hyperemic effects of sucralfate but the combination of both indomethacin and L-NNA completely abolished these effects. We conclude that sucralfate activates both the NO and PG systems that cooperate in the gastroprotective action of this drug and that NO is not involved in the protection induced by a PGE2 analog.
Konturek
S J
SJ
Institute of Physiology, University Medical School, Krakow, Poland.
Brzozowski
T
T
Majka
J
J
Czarnobilski
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000431:Ethanol; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D019335:Nitroarginine; D011453:Prostaglandins / Q000502:physiology*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000098:blood supply / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control; D013392:Sucralfate / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D011453:Prostaglandins; D011461:Prostaglandins F, Synthetic; D019335:Nitroarginine; D009569:Nitric Oxide; D000431:Ethanol; D013392:Sucralfate; C048895:nocloprost; D001120:Arginine; D007213:Indomethacin