Effects of chronic nitric oxide synthase inhibition in cold-restraint and ethanol-induced gastric mucosal damage in rats.
Gastric actions of Nw-nitro-1-arginine methyl ester (L-NAME) were investigated in rats, as this agent is a reliable nitric oxide synthase inhibitor L-NAME solutions were placed in subcutaneous osmotic minipumps which continuously released L-NAME at 0.1, 1.0, 10, or 40 mg/kg/day. L-NAME dose and time-dependently enhanced stress-induced gastric ulceration but did not affect mucosal mast cell population. Ulcerogenic actions of L-NAME were reversed by L-arginine but not by D-arginine. Ten L-NAME treatment also enhanced the ethanol-induced gastric mucosal damage, depressed gastric mucosal blood flow but did not alter gastric mucus, secretory volume, or acid output. It is concluded that in the present models, chronic nitric oxide synthase inhibition enhanced ulcerogenesis by decreasing mucosal resistance due to reduced mucosal blood perfusion. This implicates nitric oxide as a mucosal defense factor which acts in part by maintaining mucosal blood flow.
Qiu
B S
BS
Department of Medicine, Shantou University Medical College, China.
Pfeiffer
C J
CJ
Cho
C H
CH
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001783:Blood Flow Velocity; D001835:Body Weight; D003080:Cold Temperature; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013276:Stomach Ulcer / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism
D004791:Enzyme Inhibitors; D000431:Ethanol; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester