Endogenous nitric oxide modulates ethanol-induced gastric mucosal injury in rats

Abstract

Background/Aims : Endothelium-derived relaxing factor regulates vascular tone via vasodilation. The relative contribution of endogenous nitric oxide to the pathophysiology of ethanol-induced gastric mucosal microcirculatory disturbances was investigated in anesthetized rats. Methods : Macroscopic and microscopic gastric mucosal damage and gastric mucosal hemodynamics including blood flow and hemoglobin oxygen saturation (ISO 2) were assessed by pretreatment with a specific NO synthase inhibitor, N ω-nitro- l-arginine ( l-NNA), before and after intragastric administration of ethanol. Results : Pretreatment with l-NNA significantly increased macroscopic (7.7-fold) and microscopic damage caused by 30% ethanol. Concurrent administration of l-arginine, but not d-arginine, significantly reduced the increase in mucosal damage. Similar results were obtained with 60% ethanol. Pretreatment with l-NNA decreased both mucosal blood flow and ISO 2 in the basal period and enhanced decreases in both mucosal blood flow (2.7-fold) and ISO 2 (4.3-fold) induced by 30% ethanol compared with controls. Concurrent administration of l-arginine, but not d-arginine, significantly inhibited the effect of l-NNA on blood flow and ISO 2 in the basal period as well as after intragastric administration of 30% ethanol. Conclusions : Endogenous NO modulates ethanol-induced gastric mucosal injury through the regulation of gastic mucosal microcirculation.