Effect of nitric oxide on the contractile function of rat reperfused skeletal muscle

The involvement of nitric oxide (NO) in ischemia-reperfusion injury remains controversial and has been reported to be both beneficial and deleterious. The purpose of this study was to examine the contribution of NO and superoxide to skeletal muscle function using an ischemic revascularized hind limb model in rats.

Warm ischemia produced by vascular pedicle clamping was sustained for 3 h. The animals were divided into four groups according to the solution administrated: (1) saline, (2) N-methyl-L-arginine acetate (L-NMMA), (3) L-NMMA + N-(N-L-g-glutamyl-S-nitroso-l-cysteinyl)glycine (S-nitrosoglutathione), or (4) superoxide dismutase (SOD). Saline, L-NMMA, or L-NMMA + S-nitrosoglutathione was infused for the first 2 h of reperfusion. The SOD was administered as an intravenous bolus 5 min before the onset of reperfusion. Postischemic blood flow was measured by a Doppler flow meter. Muscle contractile function was determined after 24 h of reperfusion.

Postischemic blood flow was significantly decreased by the L-NMMA infusion compared with that in the saline-treated group. No significant difference in postischemic blood flow was noted in the saline-, L-NMMA + S-nitrosoglutathione-, and SOD-treated groups. Contractile function of the gastrocnemius muscle in the L-NMMA-and SOD-treated groups, but not in the L-NMMA + S-nitrosoglutathione group, was significantly better than that in the saline-treated group.

Limiting postischemic blood flow and SOD infusion are both beneficial in decreasing the ischemia-reperfusion injury of skeletal muscle. S-Nitrosoglutathione infusion following suppression of endogenous NO production does not reduce ischemia-reperfusion injury.