Nitric oxide synthase inhibition negates bombesin-induced gastroprotection

Citation
Aa. Casteneda et al., Nitric oxide synthase inhibition negates bombesin-induced gastroprotection, SURGERY, 128(3), 2000, pp. 422-428
Citations number
27
Categorie Soggetti
Surgery,"Medical Research Diagnosis & Treatment
Journal title
SURGERY
ISSN journal
00396060 → ACNP
Volume
128
Issue
3
Year of publication
2000
Pages
422 - 428
Database
ISI
SICI code
0039-6060(200009)128:3<422:NOSINB>2.0.ZU;2-I
Abstract
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.