NO is necessary and sufficient for the protection from contraction‐induced injury provided by passive‐stretch‐conditioning

Abstract

Exposing skeletal muscle to repeated stretches without activation (passive stretches) reduces the severity of injury induced by subsequent exposure to lengthening contractions (LCs). Passive stretch leads to release of nitric oxide (NO) and overexpression of neuronal nitric oxide synthase (nNOS) reduces the inflammation and membrane damage of reloading injury. We hypothesized that the NO release is necessary for the protective effects of passive-stretch-conditioning and elevated NO is sufficient to reduce injury, even in the absence of prior conditioning. Mice were untreated or treated with either the nNOS inhibitor 1-(2-trifluoromethyl-phenyl)-imidazole (TRIM) or the NOS substrate L-arginine. Extensor digitorum longus (EDL) muscles underwent 75 LCs with or without exposure to 75 passive stretches 1 hour before. Maximum isometric force, damaged fibers, and infiltrating neutrophils were measured 3 days after LCs. The deficits in isometric force, the numbers of injured fibers, and the numbers of infiltrating neutrophils were not different for passive-stretch-conditioned muscles of TRIM-treated mice or unconditioned muscles of TRIM-treated or untreated mice. For L-arginine-treated mice, both unconditioned and passive-stretch-conditioned muscles had smaller deficits in isometric force, fewer injured fibers, and fewer neutrophils compared with unconditioned muscles of untreated mice. We conclude that NO is both necessary and sufficient to reduce contraction-induced injury and that the protective effects of NO may be due to a decrease in inflammation. Supported by AG-20591.