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 endothelial-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have investigated the effects of inhibition of NO synthesis on ischemia/reperfusion 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 viability. In muscles receiving an infusion of the nitric oxide synthase inhibitor, L-NIO (30 microM), the loss of viability was reduced to 15%. Post-ischemic blood flow was increased in muscles receiving a saline infusion, 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 microM). The increase in myeloperoxidase levels (indicative of neutrophil 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 that endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival.
Phan
L H
LH
Microsurgery Research Centre, St. Vincent's Hospital, Fitzroy, Victoria, Australia.
Hickey
M J
MJ
Niazi
Z B
ZB
Stewart
A G
AG
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D007261:Infusions, Intra-Arterial; D018482:Muscle, Skeletal / Q000098:blood supply*; D009252:NADPH Dehydrogenase / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000009:adverse effects / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009952:Ornithine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D009952:Ornithine; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase