Differential activation of sympathetic discharge to skin and skeletal muscle in humans.

Abstract

The present work provides insight into the relative contribution of different mechanisms in regulating sympathetic discharge to skin and skeletal muscle in humans. Activation of sympathetic nerve activity during common behaviours such as orthostasis and exercise was shown to be highly selective, depending on the specific sympathetic outflow under study. Regarding orthostasis, data from experiments in this thesis revoked the concept that cardiopulmonary afferents only regulate muscle vascular resistance in the forearm, not in the leg. Also the concept that the cutaneous circulation is under baroreceptor control has been challenged. Unloading cardiopulmonary afferents with lower body negative pressure elicited intensity dependent increases in peroneal sympathetic discharge to skeletal muscle, and increases in forearm and calf vascular resistances. Therefore, it was concluded that cardiopulmonary afferents regulate vascular resistance in skeletal muscle of both forearm and calf, suggesting an important role for these afferents in the reflex adjustments to upright posture. In contrast to muscle sympathetic nerve activity, baroreceptor deactivation with lower body negative pressure had no effect on skin sympathetic nerve activity or skin vascular resistance. However, assumption of upright posture increased skin vascular resistance, this increase was abolished when increased vascular transmural pressure was avoided by elevating the arm. Local cutaneous nerve blockade, but not blockade of efferent sympathetic nerve traffic, abolished the vasoconstrictor response to upright posture. Based on these experiments, it was concluded that baroreceptor afferents do not regulate sympathetic vasoconstrictor outflow to the cutaneous circulation. During upright posture at normothermia cutaneous vasoconstriction is mainly driven by a local reflex. To explain activation of sympathetic outflow during exercise two theories have been proposed. One is that a "central motor command" signal emanates from the rostral brain. The other is that a contraction induced reflex arises in chemically and mechanically sensitive muscle afferents. Although animal studies have provided experimental support for both theories, studies in humans with direct recordings of muscle sympathetic nerve activity have only provided convincing evidence for the muscle afferent theory. The present experiments are the first in humans to provide direct evidence in support of the "central motor command" theory. In addition, these experiments demonstrated a highly dissociated pattern of sympathetic activation to skin and skeletal muscle. Thus, during static handgrip exercise sympathetic outflow to skin of the resting limb showed an initial burst of activity preceding the onset of tension development. This was followed by an increase in sympathetic activity that continued throughout the exercise period. Sympathetic outflow to resting muscle showed a slow pattern of response with a latent period between the onset of exercise and the onset of sympathetic activation. Stimulation of central command during neuromuscular blockade evoked large increases in skin sympathetic discharge with only minor increases in muscle sympathetic discharge. During stimulation of metaboreceptor afferents with post-handgrip muscle ischaemia, muscle sympathetic nerve activity was maintained while skin sympathetic nerve activity showed an immediate return to pre-exercise levels. These data provide evidence that during moderate levels of static exercise sympathetic activation of skin is predominantly influenced by central motor command. In contrast, sympathetic activation of muscle is to a large extent driven by feedback from metaboreceptor afferents in the working muscle.