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

我们假设，在自愿运动中，中脑多巴胺能系统在产生自主控制心血管系统的中枢命令信号方面发挥了重要作用。为了验证这一假说，我们研究了电或化学刺激中脑某些多巴胺区域，特别是腹侧被盖区(VTA)和黑质(SN)，是否引起麻醉猫和大鼠的心血管变化。刺激VTA，而不是SN，导致肢体血流量增加，提示骨骼肌血管扩张。损毁双侧VTA可钝化清醒猫自愿运动开始时中枢诱发的心率(HR)增加。由于特发性帕金森病患者已知会失去中脑中的多巴胺能神经元，因此患者在运动过程中中枢诱发的心血管反应预计会比正常受试者减少。事实上，在特发性帕金森氏病患者中，在自愿握力练习或姿势改变开始时，心率和心输出量的反应是迟钝的。另一方面，在遗传型早发性帕金森病患者中，其VTA中的多巴胺能细胞保持相对完整，其心血管反应比特发性帕金森病患者更大。这些基础和临床结果支持我们的假设，即中脑多巴胺能神经元与中枢指令信号密切相关，中枢指令信号负责在人类和清醒动物的自愿运动中进行心血管调节。

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.