CHANGES IN GASTRIC HCO3- SECRETORY RESPONSE TO N-G-NITRO-L-ARGININE METHYL-ESTER IN RATS FOLLOWING REPEATED ADMINISTRATION

The effect of repeated administration of the nitric oxide synthase inh ibitor N-G-nitro-L-arginine methyl ester (L-NAME) on gastric HCO3- sec retion was examined using ex vivo chambered stomachs of anaesthetized rats. Intravenous administration of L-NAME (5 mg/kg) increased gastric HCO3- secretion with a concomitant rise in arterial blood pressure (B P). The HCO3- stimulatory action of L-NAME diminished when rats were p retreated with L-NAME (20 mg/kg, p.o., twice daily) for 1 or 3 days an d an inverse relationship was found between the degree of secretory st imulation and the period of pretreatment. The increased BP response to L-NAME was also significantly lessened following repeated pretreatmen t; basal BP showed a stepwise increase during repeated pretreatment an d did not change at all in response to i.v. L-NAME after 3 days pretre atment. When Delta HCO3- output induced by i.v. L-NAME was plotted aga inst 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 w hen animals were pretreated with L-arginine (500 mg/kg, i.p., twice da ily) together with L-NAME. However, prostaglandin E(2) (300 mu g/kg, i .v.) caused a gastric HCO3- secretory response similar to L-NAME, rega rdless of whether rats had been pretreated with L-NAME or not. In cont rast, the attenuation by L-NAME of the acid (0.2 nmol/L HCl)-induced g astric hyperaemic response was not influenced by repeated pretreatment with L-NAME. We conclude that repeated p.o. pretreatment with L-NAME reduces the HCO3- stimulatory action of i.v. L-NAME and that this phen omenon may be explained by the lack of further elevation of BP in resp onse to i.v. L-NAME following repeated pretreatment with this agent. T hus, the stimulation of HCO3- secretion by i.v. L-NAME may be causally related with increased BP in response to this agent.