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.