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
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.