ACID-INDUCED DUODENAL MUCOSAL NITRIC-OXIDE OUTPUT PARALLELS BICARBONATE SECRETION IN THE ANESTHETIZED PIG

We recently showed the involvement of the L-arginine/nitric oxide (NO) pathway in acid-induced duodenal mucosal bicarbonate secretion in rat s. The aim of the present study was to confirm this observation in pig s by direct measurements of NO production. Experiments were performed on 16 anaesthetized pigs of both sexes treated with guanethidine (6 mg kg(-1), intravenously). A duodenal segment, devoid of pancreaticobili ary influxes, was perfused with saline and the duodenal mucosal bicarb onate secretion was calculated from continuous measurements of pH and P-CO2. The perfusate contents of NO and its oxidative product nitrite were determined by chemiluminescence, after reduction of nitrite to NO . Luminal acidification with 30 mM hydrochloric acid increased the out put of bicarbonate as well as NO to the perfusate, by 195 +/- 45% and 106 +/- 10%, respectively. These responses to acid were markedly inhib ited by adding the NO synthase inhibitor N-G-monomethyl-L-arginine (L- NMMA, 0.3 mM) to the perfusate. The inhibitory effect of L-NMMA could be reversed by administration of L-arginine (3 mM). The study presents simultaneous measurements of bicarbonate and NO outputs to a duodenal luminal perfusate. The results strongly support the view that the L-a rginine/NO pathway is involved in the acid-induced duodenal mucosal bi carbonate secretory response.