Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

Abstract

The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1 ؉ and ED2 ؉ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N -nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1 ؉ and ED2 ؉ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with watertreated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

Lipopolysaccharide‐induced monocyte chemotactic protein‐1 is enhanced by suppression of nitric oxide production, which depends on poor CD14 expression on the surface of skeletal muscle

“…It is known that NO inhibits monocyte-endothelial cell interactions 10 and the recruitment of neutrophils. 4,5 However, an NO donor has never been reported to inhibit LPS-induced MCP-1 production in skeletal muscle although it is known that LPS induces chemokine production in skeletal muscle. 11 In addition, to measure NO production, C2C12 cells were stimulated by LPS.…”

“…In fact, it was reported that skeletal muscle-derived NO production suppressed recruitment of neutrophils. 4,5 The possibility exists that skeletal muscle itself modulates the recruitment of immune cells when infection is present. However, it has not been determined whether skeletal muscle cell-derived NO production influences MCP-1 production after LPS stimulation.…”

Acute heat stress activated inflammatory signaling in porcine oxidative skeletal muscle

“…2017) and oxidative stress has been previously shown to lead to inflammatory signaling (Pizza et al. 1998). In addition, in skeletal muscle heat stress failed to increase expression of heat shock proteins, however in intestinal samples from these animals they were elevated (Pearce et al.…”

Role of nitric oxide in the local and systemic pathophysiological effects induced by Bothrops asper snake venom in mice

“…NO has been implicated in acute muscle damage in various experimental models in vivo and in cell culture. Muscle cells cocultured with both neutrophils and macrophages developed a NO-dependent cytotoxic process [32], and inhibition of NOS by L-NAME decreased the extent of muscle cell damage in an experimental model of modifi ed muscle use [33], as well as in models of muscle crush injury [34]. Furthermore, knockout mice for iNOS develop less muscle injury in a model of ischemia-reperfusion [35].…”