Effects of nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on duodenal alkaline secretory and ulcerogenic responses induced by mepirizole in rats.
The inhibition of nitric oxide (NO) production by NO synthase inhibitors stimulates HCO3- secretion in the rat duodenal mucosa. Therefore, we examined the effects of NG-nitro-L-arginine methyl ester (L-NAME, the NO synthase inhibitor) and nitroprusside (the exogenous NO donor) on the duodenal HCO3- and ulcerogenic responses in anesthetized rats. Animals were administered mepirizole (200 mg/kg, subcutaneously) for induction of duodenal ulcers, and gastric acid and duodenal HCO3- secretions were measured with or without pretreatment with L-NAME (5 mg/kg, intravenously) or nitroprusside (4 mg/kg, intravenously). Mepirizole increased acid secretion, decreased the acid-induced duodenal HCO3- secretion, and induced hemorrhagic lesions in the proximal duodenum. The inhibition of NO production by L-NAME potentiated the acid secretory response, increased the duodenal HCO3- secretion, and prevented the duodenal lesions, and these changes were all antagonized by simultaneous administration of L-arginine (200 mg/kg, intravenously) but not D-arginine. On the other hand, nitroprusside slightly reduced the acid response but further decreased the HCO3- output, resulting in aggravation of duodenal lesions induced by mepirizole. These data suggest that the inhibition of endogenous NO production by the NO synthase inhibitor L-NAME increases duodenal HCO3- secretion and protects the duodenal mucosa against acid injury.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Ohuchi
T
T
Okabe
S
S
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D004381:Duodenal Ulcer / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004840:Epirizole / Q000009:adverse effects*; D005744:Gastric Acid / Q000378:metabolism; D007419:Intestinal Secretions / Q000737:chemistry / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D009599:Nitroprusside; D009569:Nitric Oxide; D004840:Epirizole; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester