ENDOGENOUS NITRIC-OXIDE MODULATES ETHANOL-INDUCED GASTRIC-MUCOSAL INJURY IN RATS

Background/Aims: Endothelium-derived relaxing factor regulates vascula r tone via vasodilation. The relative contribution of endogenous nitri c oxide to the pathophysiology of ethanol-induced gastric mucosal micr ocirculatory disturbances was investigated in anesthetized rats. Metho ds: Macroscopic and microscopic gastric mucosal damage and gastric muc osal hemodynamics including blood flow and hemoglobin oxygen saturatio n (ISO2) were assessed by pretreatment with a specific NO synthase inh ibitor, N-omega-nitro-L-arginine (L-NNA), before and after intragastri c administration of ethanol. Results: Pretreatment with L-NNA signific antly increased macroscopic (7.7-fold) and microscopic damage caused b y 30% ethanol. Concurrent administration of L-arginine, but not D-argi nine, significantly reduced the increase in mucosal damage. Similar re sults were obtained with 60% ethanol. Pretreatment with L-NNA decrease d both mucosal blood flow and ISO2 in the basal period and enhanced de creases in both mucosal blood flow (2.7-fold) and ISO2 (4.3-fold) indu ced by 30% ethanol compared with controls. Concurrent administration o f L-arginine, but not D-arginine, significantly inhibited the effect o f L-NNA on blood flow and ISO2 in the basal period as well as after in tragastric administration of 30% ethanol. Conclusions: Endogenous NO m odulates ethanol-induced gastric mucosal injury through the regulation of gastic mucosal microcirculation.