Oxygen free radicals are implicated in the pathophysiology of ischemia-reperfusion (I/R) injury in skeletal muscle. Nitric oxide (NO) and prostaglandin E-2 (PGE(2)) are important regulators of the microcirculation in skeletal muscle. The effects of L-arginine, substrate for NO, and NG-nitro L-arginine methyl ester (L-NAME) on PGE2 synthesis, lipid peroxidation and reduced glutathione (GSH) levels was investigated in the rat gastrocnemius muscle after 3 h of reperfusion following 2 h of ischemia. Lipid peroxidation and GSH levels showed a non-significant changes in the I/R groups compared to the control group. According to these results, it can be assumed that skeletal muscle can resist 2 h of ischemia followed by 3 h of reperfusion-induced oxidative stress. PGE(2)-like activity in the gastrocnemius muscle increased in the L-NAME treated and I/R groups. L-arginine administration reversed the increase in PGE2-like activity of reperfused skeletal muscle. These findings support the conclusion that endothelium-derived PGE2 synthesis increases during reperfusion and suggest that PGE2 may have a protective role in the maintenance of endothelial function. (C) 2001 Harcourt Publishers Ltd.