Sympatho-Excitation in Heart Failure: Contribution of Skeletal Muscle Reflexes and the Protective Role of Exercise Training. Contribution of Skeletal Muscle Reflexes and the Protective Role of Exercise Training.

Skeletal muscle dysfunction in chronic heart failure (CHF) contributes to exercise intolerance and activation of the sympathetic nervous system. Exercise training has been advocated for patients with CHF and has been shown to improve quality of life and longevity. While enhanced protein degradation and oxidative stress contributes to this dysfunction exercise training of patients with CHF can reverse many of these abnormalities. The so-called "Exercise Pressor Refle" (EPR) contributes to enhanced sympatho-excitation in CHF. This chapter discusses the mechanisms that contribute to increased sensitivity of the EPR and its reduction following exercise training. In this chapter, we provide the experimental evidence that group III skeletal muscle afferent neurons are primarily responsible for this sensitization. This sensitization may be due to enhanced purinergic signaling and increased oxidative stress. Importantly, exercise training reduces the EPR sensitivity, in part, by upregulation of the Transient Receptor Potential Vanilloid 1 receptor (TRPV1) and downregulation of P2X3 receptors in skeletal muscle of animals with CHF.