In vivo evidence that endogenous dopamine modulates sympathetic activity in man

Dopamine receptors type 2 (D2)-like receptor blockers cause an increase in the norepinephrine response to intense physical exercise. However, during i ntense physical exercise, D2-like antagonists also cause an increase in the epinephrine response, which itself might cause an increase in plasma norep inephrine through the activation of beta 2 presynaptic receptors. Therefore , we evaluated the effect of domperidone, a D2-like antagonist, on the nore pinephrine response to physical exercise in 6 Addison patients (3 were adre nalectomized and 3 had adrenal tuberculosis). In these patients, the norepi nephrine increase observed during exercise was significantly higher after t he administration of domperidone than a placebo (F=4,328; P<0.001). Because peripheral plasma norepinephrine does not reflect the sympathetic tone to the heart accurately, we evaluated the effect of domperidone administration (20 mg orally) on the sympathovagal balance, which was measured by the rat io between the high- and low-frequency components of heart rate variability , in 9 normal volunteers in the supine and sitting positions. When compared with placebo, domperidone caused a significant increase in the low/high fr equency ratio (P<0.05) in the silting position without modifying basal and stimulated norepinephrine plasma levels or blood pressure. These data suppo rt a role for endogenous dopamine in modulating norepinephrine release by h uman sympathetic nerves in vivo.