Changes in gastric HCO-3 secretory response to NG-nitro-L-arginine methyl ester in rats following repeated administration.

The effect of repeated administration of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on gastric HCO-3 secretion was examined using 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 L-NAME diminished when rats were pretreated with L-NAME (20 mg/kg, p.o., twice daily) for 1 or 3 days and an inverse relationship was found between the degree of secretory stimulation and the period of pretreatment. The increased BP response to L-NAME was also significantly lessened following repeated pretreatment; basal BP showed a stepwise increase during repeated pretreatment and did not change at all in response to i.v. L-NAME after 3 days pretreatment. When delta HCO-3 output induced by i.v. L-NAME was plotted against delta BP (from basal values) during repeated pretreatment with L-NAME, a significant relationship was found between these two factors. The reduction in the HCO3 secretory response to L-NAME was restored when animals were pretreated with L-arginine (500 mg/kg, i.p., twice daily) together with L-NAME. However, prostaglandin E2 (300 micrograms/kg, i.v.) caused a gastric HCO-3 secretory response similar to L-NAME, regardless of whether rats had been pretreated with L-NAME or not. In contrast, the attenuation by L-NAME of the acid (0.2 nmol/L HCl)-induced gastric hyperaemic response was not influenced by repeated pretreatment with L-NAME. We conclude that repeated p.o. pretreatment with L-NAME reduces the HCO-3 stimulatory action of i.v. L-NAME and that this phenomenon may be explained by the lack of further elevation of BP in response to i.v. L-NAME following repeated pretreatment with this agent. Thus, the stimulation of HCO-3 secretion by i.v. L-NAME may be causally related with increased BP in response to this agent.