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Effects of nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester on duodenal alkaline secretory and ulcerogenic responses induced by mepirizole in rats

  • Esophageal, Gastric, And Duodenal Disorders
  • Published:
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Abstract

The inhibition of nitric oxide (NO) production by NO synthase inhibitors stimulates HCO −3 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 HCO −3 and ulcerogenic responses in anesthetized rats. Animals were administered mepirizole (200 mg/kg, subcutaneously) for induction of duodenal ulcers, and gastric acid and duodenal HCO −3 secretions were measured with or without pretreatment withl-NAME (5 mg/kg, intravenously) or nitroprusside (4 mg/kg, intravenously). Mepirizole increased acid secretion, decreased the acid-induced duodenal HCO −3 secretion, and induced hemorrhagic lesions in the proximal duodenum. The inhibition of NO production byl-NAME potentiated the acid secretory response, increased the duodenal HCO −3 secretion, and prevented the duodenal lesions, and these changes were all antagonized by simultaneous administration ofl-arginine (200 mg/kg, intravenously) but notd-arginine. On the other hand, nitroprusside slightly reduced the acid response but further decreased the HCO −3 output, resulting in aggravation of duodenal lesions induced by mepirizole. These data suggest that the inhibition of endogenous NO production by the NO synthase inhibitorl-NAME increases duodenal HCO −3 secretion and protects the duodenal mucosa against acid injury.

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Authors and Affiliations

  1. From the Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, 607, Kyoto, Japan

    Koji Takeuchi PhD, Tomohisa Ohuchi MA & Susumu Okabe PhD

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  1. Koji Takeuchi PhD
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  2. Tomohisa Ohuchi MA
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  3. Susumu Okabe PhD
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Takeuchi, K., Ohuchi, T. & Okabe, S. Effects of nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester on duodenal alkaline secretory and ulcerogenic responses induced by mepirizole in rats. Digest Dis Sci 40, 670–677 (1995). https://doi.org/10.1007/BF02064389

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  • DOI: https://doi.org/10.1007/BF02064389

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