Eccentric exercise induces nitric oxide synthase expression through nuclear factor- B modulation in rat skeletal muscle

Lima-Cabello E, Cuevas MJ, Garatachea N, Baldini M, Almar M, González-Gallego J. Eccentric exercise induces nitric oxide synthase expression through nuclear factorB modulation in rat skeletal muscle. J Appl Physiol 108: 575–583, 2010. First published December 31, 2009; doi:10.1152/japplphysiol.00816.2009.—This study aimed to investigate the effect of eccentric exercise on the expression of the different nitric oxide synthase (NOS) isoforms in rat deep vastus lateralis muscle. Twenty-four rats were allocated to four experimental groups: rested control group, acutely exercised group after an intermittent downhill protocol for 90 min, acutely exercised group treated with pyrrolidine dithiocarbamate (100 mg/kg ip) for 24 and 1 h before the acute exercise bout, and acutely exercised group with a previous submaximal eccentric training of 8 wk. Acutely exercised rats showed increased levels of protein tyrosine nitration, NFB binding, and phospho-I B content. A significant increase was observed in mRNA level and protein content of neuronal NOS, inducible NOS, and endothelial NOS. The binding of NFB to the NOS isoform promoters, measured by a chromatin immunoprecipitation assay, was undetectable in rested rats, whereas it was evident in acutely exercised animals. All of these effects were partially abolished by pyrrolidine dithiocarbamate treatment and by training. In summary, our findings provide a direct link between the NFB signaling cascade and NOS expression in skeletal muscle following eccentric exercise and suggest a modulation of the expression of the three NOS isoforms by this transcription factor.