Nephrosis aggravates HCl-ethanol-induced gastric lesions in rats

This study was performed to evaluate the effect of nephrosis on gastric lesions in the rats. A single i.v. injection of daunomycin (12 mg/kg) into rats produced severe proteinuria and hypercholesterolemia on the 20th and 40th days after the administration. The severity of HCl-ethanol-induced gastric lesions was significantly greater in nephrotic rats than in control animals on the 20th and 40th days. The gastric mucosal blood flow on the 40th day was significantly lower in nephrotic rats. Pretreatment of normal rats with N(omega-)nitro-L-arginine or N-omega-nitro-L-arginine methyl ester, a nitric oxide (NO) synthase inhibitor, methylene blue, a guanylate cyclase inhibitor, or phenylephrine, a vasoconstrictor, significantly aggravated the HCl-ethanol-induced gastric lesions and reduced the blood flow. When N-omega-nitro-L-arginine methyl ester was given to nephrotic rats on the 40th day, it further increased the aggravation of the gastric lesions caused by nephrosis. These results suggest that the aggravation of HCl-ethanol-induced gastric lesions observed in nephrotic rats may be, at least in part, related to the decrease in the release of NO from endothelial cells.