Effect of a NOS Inhibitor, L‐NMMA, on the Contractile Function of Reperfused Skeletal Muscle

ABSTRACT

The authors investigated the effect of N^G-monomethyl-L-arginine acetate (L-NMMA), a nitric oxide synthase (NOS) inhibitor, on the contractile function of skeletal muscle following ischemia/reperfusion (I/R) injury. The extensor digitorum longus (EDL) muscles of 50 rats were divided into seven groups. Contractile function in non-ischemic EDL did not change statistically significantly with L-NMMA infusion. I/R (1.5 hr I and 3 hr R) significantly decreased EDL contractile function, with an average maximal twitch force of 56 percent of the contralateral normal muscle force and isometric tetanic contractile forces between 47 and 84 percent at four different stimulation frequencies. Following L-NMMA administration at three different dosages, contractile function of I/R muscle decreased in a dose-dependent manner. The highest dosage of L-NMMA (10 μmol/min) reduced the average maximal twitch force to 15 percent and the isometric tetanic contractile forces to between 10 to 23 percent. Histologic evaluation revealed increased edema, neutrophil infiltration, and muscle-fiber necrosis in L-NMMA-infused EDL, compared to the controls. 1) Skeletal muscle contractile function was dose-dependently decreased with the administration of L-NMMA during I/R. 2) The concentrations of L-NMMA used in this study did not influence the function of non-ischemic EDL. These findings suggest that reduction of NO production during I/R is damaging to skeletal muscle function and would impair successful functional outcomes in microsurgical replantation.