Background. Bombesin prevents gastric injury primarily by the release of en
dogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitri
c oxide synthase inhibition, which implicates a role for nitric oxide as a
protective mediator Because both endothelial and inducible isoforms of this
enzyme can play a role in mucosal defense, this study was done to examine
the contrasting effects of 2 nitric oxide synthase inhibitors on bombesin-i
nduced gastroprotection.
Methods. Rats were given subcutaneous saline or bombesin (10-100 mu g/kg) 3
0 minutes before they received a I-mt orogastric bolus of acidified ethanol
(150 mmol/L of hydrochloric acid/50% ethanol) and rats were killed 5 minut
es later for assessment of macroscopic injury (mm(2)). Gastric mucosal bloo
d flow was measured by laser Doppler. Endothelial, neural, and inducible ni
tric oxide synthase were assessed by using Western immunoblot.
Results. Bombesin decreased gastric mucosal damage, and dose-dependently in
creased blood flow when compared with saline-treated rats. Endothelial but
not neural or inducible nitric oxide synthase immunoreactivity was increase
d by bombesin. In additional studies, intraperitoneal administration of N-G
-nitro-L-arginine methyl ester (L-NAME, 5-10 mg/kg), a nonselective nitric
oxide synthase inhibitor; negated bombesin-induced gastroprotection and hyp
eremia, whereas the selective inducible inhibitor aminoguanidine (45 mg/kg)
did not. Subcutaneous (SC) L-arginine (300 mg/kg), but not D-arginine, abo
lished the effects of L-NAME.
Conclusions. Taken together, these data suggest that nitric oxide produced
by the endothelial isoform of nitric oxide synthase plays an important role
in mediating the gastroprotective and hyperemic actions associated with bo
mbesin.