Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle

Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia Submitted 15 May 2006 ; accepted in final form 2 August 2006 The purpose of this study was to determine whether nitric oxide synthase (NOS) inhibition decreased basal and exercise-induced skeletal muscle mitochondrial biogenesis. Male Sprague-Dawley rats were assigned to one of four treatment groups: NOS inhibitor N G -nitro- L -arginine methyl ester ( L -NAME, ingested for 2 days in drinking water, 1 mg/ml) followed by acute exercise, no L -NAME ingestion and acute exercise, rest plus L -NAME, and rest without L -NAME. The exercised rats ran on a treadmill for 53 ± 2 min and were then killed 4 h later. NOS inhibition significantly ( P < 0.05; main effect) decreased basal peroxisome proliferator-activated receptor- coactivator 1 (PGC-1 ) mRNA levels and tended ( P = 0.08) to decrease mtTFA mRNA levels in the soleus, but not the extensor digitorum longus (EDL) muscle. This coincided with significantly reduced basal levels of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and COX enzyme activity following NOS inhibition in the soleus, but not the EDL muscle. NOS inhibition had no effect on citrate synthase or -hydroxyacyl CoA dehydrogenase activity, or cytochrome c protein abundance in the soleus or EDL. NOS inhibition did not reduce the exercise-induced increase in peroxisome proliferator-activated receptor- coactivator 1 (PGC-1 ) mRNA in the soleus or EDL. In conclusion, inhibition of NOS appears to decrease some aspects of the mitochondrial respiratory chain in the soleus under basal conditions, but does not attenuate exercise-induced mitochondrial biogenesis in the soleus or in the EDL. contraction; metabolic regulation; peroxisome proliferator-activated receptor- coactivator 1 Address for reprint requests and other correspondence: G. Wadley, Dept. of Physiology, The Univ. of Melbourne, Parkville 3010, Australia (e-mail: gdwadley{at}unimelb.edu.au )