Central command generation during exercise: role of the brain dopaminergic system

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We hypothesized that the midbrain dopaminergic system played an important role in producing central command signal for autonomic control of the cardiovascular system during voluntary exercise. To examine this hypothesis, we studied whether electrical or chemical stimulation of some dopamine areas in the midbrain, particularly the ventral tegmental area (VTA) and substantial nigra (SN), evoked the cardiovascular changes in anesthetized cats and rats. The stimulation of VTA, but not SN, caused an increase in limb blood flow, suggesting vasodilatation of skeletal muscle blood vessels. Lesion of bilateral VTA blunted the centrally-induced increase in heart rate (HR) at the beginning of voluntary exercise in conscious cats. Since idiopathic Parkinson's disease patients are known to lose dopaminergic neurons in the midbrain, the centrally-induced cardiovascular responses during exercise in the patients were expected to reduce than those in normal subjects. Indeed, the responses in HR and cardiac output at the beginning of voluntary handgrip exercise or postural change were blunted in idiopathic Parkinson's disease patients. On the other hand, in the genetic type of early-onset Parkinson's disease patients, whose dopaminergic cells in VTA remained relatively intact, the cardiovascular responses were greater than those in idiopathic Parkinson's disease patients. These basic and clinical findings were in favor of our hypothesis that the midbrain dopaminergic neurons are closely linked with central command signal that is responsible for the cardiovascular adjustment during voluntary exercise in humans and conscious animals.