OVEREXPRESSED NITRIC-OXIDE SYNTHASE IN PORTAL-HYPERTENSIVE STOMACH OFRAT - A KEY TO INCREASED SUSCEPTIBILITY TO DAMAGE

Background & Aims: Portal hypertension predisposes gastric mucosa to i ncreased injury, The aim of this study was to determine whether overex pression of constitutive nitric oxide synthase (cNOS) is responsible f or increased susceptibility of portal-hypertensive (PHT) gastric mucos a to damage, Methods: In gastric specimens from PHT and sham-operated rats, cNOS messenger RNA expression was determined by Northern blottin g and cNOS protein expression by Western blotting, immunohistochemistr y, and enzyme activity assay, Extent of ethanol-induced gastric mucosa l necrosis, mucosal blood flow, and gastric NOS activity in PHT and sh am-operated rats was determined after administration of N-omega-nitro- L-arginine methyl ester (L-NAME) or saline. Results: cNOS messenger RN A level, cNOS enzyme activity, and fluorescence signals for cNOS were increased significantly in PHT vats compared with controls, Inhibition of overexpressed cNOS by L-NAME (5 mg/kg) significantly reduced ethan ol-induced mucosal necrosis and normalized blood flow in PHT gastric m ucosa, whereas this dose of L-NAME significantly increased mucosal nec rosis in sham-operated rats, Conclusions: Portal hypertension activate s the cNOS gene with overexpression of cNOS protein in endothelia of g astric mucosal vessels, Excessive NO production by overexpressed cNOS may play an important role in the increased susceptibility of PHT gast ric mucosa to damage.