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 intense physical exercise, D2-like antagonists also cause an increase in the epinephrine response, which itself might cause an increase in plasma norepinephrine through the activation of beta2 presynaptic receptors. Therefore, we evaluated the effect of domperidone, a D2-like antagonist, on the norepinephrine response to physical exercise in 6 Addison patients (3 were adrenalectomized and 3 had adrenal tuberculosis). In these patients, the norepinephrine increase observed during exercise was significantly higher after the 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 ratio 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 frequency ratio (P<0.05) in the sitting position without modifying basal and stimulated norepinephrine plasma levels or blood pressure. These data support a role for endogenous dopamine in modulating norepinephrine release by human sympathetic nerves in vivo.
Mannelli
M
M
Department of Clinical Pathophysiology, Endocrine Unit, University of Florence, Italy. m.mannelli@dfc.unifi.it
Ianni
L
L
Lazzeri
C
C
Castellani
W
W
Pupilli
C
C
La Villa
G
G
Barletta
G
G
Serio
M
M
Franchi
F
F
D000307:Adrenal Gland Diseases / Q000378:metabolism / Q000503:physiopathology; D000328:Adult; D018592:Cross-Over Studies; D004294:Domperidone / Q000494:pharmacology*; D004298:Dopamine / Q000097:blood / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D005082:Physical Exertion / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000502:physiology*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D004294:Domperidone; D004298:Dopamine; D009638:Norepinephrine