NITRIC-OXIDE SYNTHASE INHIBITOR, NITRO-IMINOETHYL-L-ORNITHINE, REDUCES ISCHEMIA-REPERFUSION INJURY IN RABBIT SKELETAL-MUSCLE

Nitric oxide (NO), originally identified as the mediator of endothelia l-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have invest igated the effects of inhibition of NO synthesis on ischemia/reperfusi on injury in the rabbit rectus femoris muscle. Three and a half hours of ischemia and 24 hours of reperfusion resulted in a 56% loss of viab ility. In muscles receiving an infusion of the nitric oxide synthase i nhibitor, L-NIO (30 mu M), the loss of viability was reduced to 15%. P ost-ischemic blood flow was increased in muscles receiving a saline in fusion, whereas there was a marked decrease in blood flow for at least the first 60 minutes of reperfusion in muscles treated with L-NIO (30 mu M). The increase in myeloperoxidase levels (indicative of neutroph il accumulation) following 24 hours of reperfusion was attenuated with L-NIO infusion by approximately 50% and the reperfusion-induced edema was also attenuated in L-NIO treated muscle. These findings suggest t hat endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival. (C) 1994 Wiley-Liss, Inc.