Abstracts
1999 Digestive Disease Week

# 2195 NITRIC OXIDE SYNTHASE INHIBITION NEGATES BOMBESIN INDUCED GASTROPROTECTION.
A Castaneda, L Chang, David W Mercer, Univ of Texas Med Sch, Houston, TX

Bombesin prevents gastric injury by release of endogenous gastrin. Gastroprotection by exogenous gastrin is negated by nitric oxide synthase (NOS) inhibition implicating a role for nitric oxide as a protective mediator. Thus, it was our hypothesis that nitric oxide would also mediate the ability of bombesin to maintain gastric mucosal integrity.. Because some evidence suggests that both the constitutive and the inducible isoforms of NOS play a role in gastric mucosal defense, this study was done to examine the effects of two different NOS inhibitors on bombesin induced gastroprotection. Conscious female rats were given either subcutaneous bombesin (100 mg/kg) or saline concurrently with a NOS inhibitor for 30 minutes while controls received vehicle. NOS inhibition was accomplished with either the nonselective NOS inhibitor, N8-nitro-L-argininemethylester (L-NAME; 5 mg/kg SC) or aminoguanidine (AG: 45 mg/kg IP), which is more selective for the inducible isoform of NOS. Following a 30 minute pretreatment, gastric injury was induced with a 1 ml orogastric bolus of acidified ethanol (150 mM hydrochloric acid/50% ethanol). Rats were killed 5 minutes later and the total area (mm2) of macroscopic gastric injury determined. In other rats, the reversibility of NOS inhibition was assessed by giving rats either L- or D-arginine (300 mg/kg SC)concurrently with the other pretreatments. Data are expressed as mean ± SE (n³ 5/group; ANOVA). As shown, L-NAME, but not AG, negated bombesin induced gastroprotection. L-arginine, but not D-arginine, abolished this effect of L-NAME (26±9*;127±20 vs. 108±20 mm2, *p<0.05). These data suggest that nitric oxide produced by the constitutive isoform of NOS plays an important role in mediating the gastroprotective actions associated with bombesin.

Pretreatment	Damage (mm2)
Saline/Saline Saline/Bombesin 22±8*	118±21 *p<0.001 vs Saline/Saline
L-NAME/Saline	135±23
L-NAME/Bombesin AG/Saline	108±20**    **p<0.001 vs Saline/Bombesin 112±19
AG/Bombesin 17±7*** ***p<0.001	vs AG/Saline

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