Muscle Reflex Control of Sympathetic Nerve Activity in Heart Failure: the Role of Exercise Conditioning

Muscle reflex control of sympathetic nerve activity has been an area of considerable investigation. During exercise, the capacity of the peripheral vasculature to dilate far exceeds the maximal attainable levels of cardiac output. The activation of sympathetic nervous system and engagement of the myogenic reflex serve as the controlling influence between the heart and the muscle vasculature to maintain blood pressure (BP). Two basic theories of neural control have evolved. The first termed "central command", suggests that a volitional signal emanating from central motor areas leads to increased sympathetic activation during exercise. According to the second theory the stimulation of mechanical and chemical afferents in exercising muscle lead to engagement of the "exercise pressor reflex". Some earlier studies suggested that group III muscle afferent fibers are predominantly mechanically sensitive whereas unmyelinated group IV muscle afferents respond to chemical stimuli. In recent years new evidence is emerging which challenges the concept of functional differentiation of muscle afferents as well as the classic description of muscle "mechano" and "metabo" receptors. Studies measuring concentrations of interstitial substances during exercise suggest that K(+) and phosphate, but not H(+) and lactate, may be important muscle afferent stimulants. The role of adenosine as a muscle afferent stimulant remains an area of debate. There is strong evidence that sympathetic vasoconstriction due to muscle reflex engagement plays an important role in restricting blood flow to the exercising muscle. In heart failure (HF), exercise leads to premature fatigue and accumulation of muscle metabolites resulting in a greater degree of muscle reflex engagement and in the process further decreasing the muscle blood flow. Conditioning leads to an increased ability of the muscle to maintain aerobic metabolism, lower interstitial accumulation of metabolites, less muscle reflex engagement and a smaller sympathetic response. Beneficial effects of physical conditioning may be mediated by a direct reduction of muscle metaboreflex activity or via reduction of metabolic signals activating these receptors. In this review, we will discuss concepts of flow and reflex engagement in normal human subjects and then contrast these findings with those seen in heart failure (HF). We will then examine the effects of exercise conditioning on these parameters in normal subjects and those with congestive heart failure (CHF).