Regulation of muscle sympathetic nerve activity during exercise in humans

Recent investigations using direct (microneurographic) recordings of MSNA have provided a substantial amount of new information on the regulation of sympathetic nervous system control of nonactive skeletal muscle blood flow during exercise in humans. Some of the new conclusions from these studies discussed in this review include: 1. The direction, pattern and magnitude of the MSNA response to exercise depend on the collective influence of a number of factors, including the mode (isometric or rhythmic), intensity, and duration of the exercise, the size of the contracting muscle mass, and possibly the level of conditioning (physical training) of the exercising muscles. The MSNA response also appears to be tightly coupled with the onset and progression of muscle fatigue, at least during sustained, isometric contractions. 2. Increases in MSNA evoked during exercise with the arms are fairly uniform among different skeletal muscle nerves, and these responses correlate strongly with changes in venous plasma norepinephrine concentrations, limb vascular resistance and arterial blood pressure. Thus, increases in this neural activity during exercise are associated with the expected physiological responses. 3. The MSNA response to the same level of exercise varies markedly among healthy subjects but appears to be consistent over time within a particular subject. 4. The muscle metaboreflex (muscle chemoreflex) is the primary-mechanism by which MSNA is stimulated during small-muscle, isometric exercise in humans. In contrast, central command has a relatively weak influence on MSNA during this type of exercise. 5. Muscle metaboreflex-stimulation of MSNA also occurs during dynamic exercise, but only at or above moderate, submaximal intensities (i.e., not during mild exercise). 6. Muscle metaboreflex-evoked increases in MSNA during exercise are strongly associated with glycogenolysis and the consequent cellular accumulation of hydrogen ions in the contracting muscles. 7. Sympathoinhibitory cardiopulmonary reflexes do not appear to modulate the MSNA responses to isometric exercise in the healthy human. However, arterial baroreflexes exert a potent inhibitory effect on MSNA during this form of exercise. The mechanisms involved in the regulation of MSNA during large-muscle, dynamic leg exercise is an important topic for future investigations, as is the relationship between MSNA and sympathetic outflow to other regional circulations (e.g., heart, viscera, skin) during various forms of exercise.