Reduction in Gastric Bicarbonate Secretory Response Induced by NG-Nitro-l -Arginine Methyl Ester Following Repeated Administration in Rats

Abstract

Gastric HCO 3 - secretory response induced by the nitric oxide (NO) synthase inhibitor, NG-nitro-targinine methyl ester (l-NAME), was examined in rats before and after the repeated administration of this agent. HCO 3 - secretion was determined in ex-vivo chambered stomachs of anaesthetized rats. Intravenous administration of l-NAME (5 mg/kg) increased gastric HCO 3 - secretion with a concomitant rise in arterial blood pressure (BP). The HCO 3 - stimulatory action of iv l-NAME diminished when they were pretreated with l-NAME (20 mg/kg × 2, po) for 1 or 3 days, and an inverse relationship was found between the degree of stimulation and the period of treatment. The increased BP response to iv l-NAME was also significantly lessened following repeated administration; the basal BP showed a step-wise increase during treatment and did not change at all in response to iv l-NAME after 3 days treatment. When ΔHCO 3 - output induced by iv l-NAME was plotted against ABP change during repeated treatment with l-NAME po, a significant relationship was found between these two factors. The reduction of HCO 3 - response to iv l-NAME was significantly restored when the animals were given l-arginine (500 mg/kg × 2 ip) simultaneously with pot-NAME. However, prostaglandin E2 (300 µg/kg iv) caused a gastric HCO 3 - response similar in degree regardless of whether the animals were pretreated with l-NAME po or not. These results suggest that: (I) the repeated po treatment with l-NAME diminishes the HCO 3 - stimulatory action of iv l-NAME; (2) this phenomenon may be explained by the lack of further elevation of blood pressure to iv l-NAME following the repeated treatment; and (3) the stimulation of HCO 3 - secretion by iv l-NAME may be causally related to the increased blood pressure response to this agent.