Endogenous dopamine (DA) and DA2 receptors: a mechanism limiting excessive sympathetic-adrenal discharge in humans

Abstract

We studied the effects of presynaptic dopamine (DA) 2 receptor blockade on the sympathetic-adrenal response to graded exercise in seven normal men. DA2 receptor blockade was achieved by means of domperidone (DMP) administration. The exercise consisted of progressive cycling activity, from 30-80% of the predetermined maximal oxygen consumption for each man. Systolic, diastolic, and mean arterial pressures; heart rate; and plasma norepinephrine (NE), epinephrine (E), PRL, glucose, lactate, FFA, sodium, potassium, cortisol, and PRA were measured at rest, during exercise, and during recovery after placebo or DMP administration. Graded exercise caused significant increases in systolic and mean arterial pressures and plasma NE, E, lactate, sodium, potassium, FFA, cortisol, and PRA. DMP administration before exercise caused a significant increase in plasma PRL (P = 0.0009), a greater increase in plasma NE at the end of the exercise (P = 0.002), and an overall increase in plasma E (P = 0.02) and FFA (P = 0.02) concentrations. These results strongly suggest that endogenous DA limits catecholamine release during sympathetic-adrenal stimulation by activating DA2 receptors.