Nitric oxide synthase inhibition prevents activity‐induced NFAT nuclear accumulation and skeletal muscle adaptation

Abstract

Involvement of calcineurin/NFAT signaling in the regulation of skeletal muscle myosin heavy chain (MHC)‐based fast‐to‐slower isoform adaptations (F‐S) is recognized. Less is known about the role nitric oxide (NO) plays in this process.OBJECTIVETo investigate the necessity of NO in activity‐induced skeletal muscle F‐S in vivo.METHODSEndogenous NO production was blocked by administering L‐NAME (0.75 mg ml−1; ~100 mg kg−1 day−1) during 0, 1, 2, 5 or 10 days of chronic low‐frequency stimulation (CLFS; 10 Hz, 12 h d−1) applied to the tibialis anterior and extensor digitorum longus muscles of rats (L‐Stim; n=6 each group). Control rats received only CLFS (Stim; n=6 each group).RESULTSCLFS induced increases in NFATc1 nuclear localization in Stim, which did not occur in L‐Stim at any time point. These results were confirmed by western blot analyses. Moreover, MHC mRNA, protein and fibre type analyses revealed CLFS‐induced F‐S occurred in Stim, but were completely abolished in L‐Stim.CONCLUSIONSNO may be regulating activity‐induced MHC‐based F‐S at the transcriptional level via NFAT nuclear accumulation in vivo. *Authors contributed equally. Funded by NSERC, AHFMR, CIHR and CRC.