Title

 

Authors

N. Sullo¹, M. Matteis¹, F. Roviezzo², S. De Rosa¹, G. Cirino², F. Rossi¹ and B.D’Agostino^1
1Dept. of Experimental Medicine, Sect. of Pharmacology, Second University of Naples, Italy
²Dept. of ExperimentalPharmacology, University “Federico II” of Naples, Italy 

 

Abstract

Exercise limitation that results in lower quality of life, in COPD patients, has been traditionally explained by the increased work of breathing and dynamic hyperinflation (Mostert R et al., 2000), even if several studies have clearly shown that skeletal muscle dysfunction is often a very significant contributor to exercise limitation (Agustí AG et al., 2003; Wouters EF et al., 2002). The impact of skeletal muscle dysfunctionis clinically relevant and its analysis may contribute to the better understanding and management of the disease. The precise cellular and molecular mechanisms leading to muscle dysfunction in pulmonary emphysema are unclear. Aim of this study was to investigate the skeletal muscle oxidative metabolism, before and following a long-acting beta agonists (LABA) aerosol exposure, in an animal model of pulmonary emphysema. C57 B1/6J and its congenic pallid mice of  8-12 and 16 months of age were exposed to saline or formoterol aerosol challenge. Morphological and morphometrical studies together to evaluations of mitochondrial ADP stimulated-respiration and cytochrome oxidase activity on skeletal muscle were performed. Moreover, mediators linked to muscle mithocondrial biogenesis and function as well as TNF-α and PGC-1α were also evaluated. The lungs of pallid mice did not show pathologic changes and appeared normal at histologic examinationup to 8 months of age, while at 12 and 16 months of age they showed patchy areas of air space enlargements with destruction of alveolar septa. No significant differences were observed in basal values of mitochondrial skeletal muscle oxidative processes between C57 and pallid mice. LABA exposure significantly improved mitochondrial skeletal muscle oxidative processes in 12 and 16 months old pallid mice. Finally, significant increase of PGC-1α m-RNA expression, while no alterations of TNF-α levels in skeletal muscles of  12- and 16-month old pallid mice, following LABA exposure, were observed.In conclusion, inthe present study we documented that a LABA exposure, such as formoterol, may improve mitochondrial skeletal muscle oxidative processesthrough an action on PGC-1α at skeletal muscle level. However, further studies on mitochondria skeletal muscle oxidative processes are required to better understanding the mechanism(s) underlying muscular LABA effects.
 
Mostert R et al., (2000). Respir Med  94: 859–67.
Agustí AG et al., (2003).Eur RespirJ  21: 347-360.
Wouters EF et al., (2002). Chest 121: 127S–130S.