EFFECTS OF ENDOTOXIN ON GASTRIC INJURY FROM LUMINAL IRRITANTS IN RATS- POTENTIAL ROLES OF NITRIC-OXIDE

The expression and function of inducible nitric oxide synthase (iNOS) in the stomach is unclear. This study assessed the effects of endotoxi n on rat gastric iNOS expression and its Pole in gastric injury from l uminal irritants. In conscious rats, a 5-h treatment with intraperiton eal lipopolysaccharide (LPS; 1-20 mg/kg) dose dependently increased ga stric mucosal iNOS immunoreactivity and increased gastric luminal nitr ate and nitrite accumulation (Griess reaction). LPS also increased gas tric luminal fluid accumulation and reduced macroscopic gastric injury from orogastric acidified ethanol. Aminoguanidine (45 mg/kg) did not prevent LPS-induced gastroprotection or gastric fluid accumulation. N- G-nitro-L-arginine methyl ester increased gastric luminal fluid and ca used macroscopic gastric injury when given with LPS. Using an anesthet ized preparation followed by removal of luminal fluid, LPS reduced gas tric mucosal blood flow and exacerbated gastric injury from either aci dified ethanol or acidified taurocholate, an effect that was negated b y aminoguanidine. These data indicate that in conscious rats, the gast roprotective effect of endotoxin is dependent on constitutive NOS but not iNOS activity. However, the inducible isoform participates in the ability of endotoxin to exacerbate gastric injury from luminal irritan ts in the anesthetized rat.