Autonomic dysfunction in muscular dystrophy: a theoretical framework for muscle reflex involvement

Abstract

Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy.

Keywords: cardiovascular disease; exercise; muscle afferents; muscular dystrophy; parasympathetic nerve activity; sympathetic nerve activity.

Figure 1

Theoretical model of factors that could influence exercise pressor reflex function in muscular dystrophy. During muscle contraction, the exercise pressor reflex is engaged upon stimulation of receptors which activate mechanically and metabolically sensitive afferent fibers innervating skeletal muscle. Sensory signals from these fibers are processed within autonomic control centers in the brainstem evoking decreases in parasympathetic nerve activity to the heart and increases in sympathetic nerve activity to the heart, adrenal gland, and vasculature of skeletal muscle, kidneys, and the splanchnic region. Numerous changes that occur with the pathogenesis of muscular dystrophy maintain the potential to both enhance and depress exercise pressor reflex activity. EPR, exercise pressor reflex; MD, muscular dystrophy; PSNA, parasympathetic nerve activity; SNA, sympathetic nerve activity.