Role of endogenous nitric oxide and prostaglandin in duodenal bicarbonate response induced by mucosal acidification in rats

Duodenal HCO3- secretion increases in response to mucosal acidification by luminal acid. Although this process is known to be mediated by endogenous p rostaglandins (PGs), the role of nitric oxide (NO) in this response has bee n little studied. We examined the effects of indomethacin and N-G-nitro-L-a rginine methyl ester (L-NAME) on the acid-induced HCO3- secretion in the ra t duodenum, together with those on PGE(2) generation as well as luminal rel ease of NO metabolites (NOx). A proximal duodenal loop was perfused with sa line, and the HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Mucosal acidification was performed by exposing t he loop to 10 or 100 mM HCl for 10 min. Acidification of the duodenal mucos a stimulated the HCO3- secretion, with concomitant increase of mucosal PGE( 2) contents and luminal release of NOx, the response being much greater in case of 100 mM HCl. Indomethacin significantly inhibited the acid-induced H CO3- secretion as well as the PGE(2) biosynthetic response, without influen ce on the NOx release. Pretreatment of the animals with L-NAME attenuated b oth the increase of mucosal PGE, contents and luminal release of NOx follow ing the acidification, resulting in a marked inhibition of the acid-induced HCO3- response, and these effects were significantly antagonized by coadmi nistration of L-arginine. Duodenal HCO3- secretion was also increased by mu cosal exposure to NOR-3 (a NO donor), with concomitant increase of PGE(2) g eneration, but these effects were mitigated in the presence of indomethacin . In addition, the duodenal damage caused by mucosal perfusion with 100 mM HCl for 4 hr was markedly aggravated by pretreatment with L-NAME as well as indomethacin. These results suggest that both endogenous NO and PGs are in volved in the mechanism for the acid-induced duodenal HCO3- secretion, and that NO may increase the HCO3- secretion by stimulating PG generation.