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

Citation
S. Sugamoto et al., Role of endogenous nitric oxide and prostaglandin in duodenal bicarbonate response induced by mucosal acidification in rats, DIG DIS SCI, 46(6), 2001, pp. 1208-1216
Citations number
31
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
DIGESTIVE DISEASES AND SCIENCES
ISSN journal
01632116 → ACNP
Volume
46
Issue
6
Year of publication
2001
Pages
1208 - 1216
Database
ISI
SICI code
0163-2116(200106)46:6<1208:ROENOA>2.0.ZU;2-B
Abstract
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.