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(Hypertension. 1999;34:398-402.)
© 1999 American Heart Association, Inc.

Scientific Contributions

In Vivo Evidence That Endogenous Dopamine Modulates Sympathetic Activity in Man

Massimo Mannelli; Lucia Ianni; Chiara Lazzeri; Walter Castellani; Cinzia Pupilli; Giorgio La Villa; Giuseppe Barletta; Mario Serio; Franco Franchi

From the Department of Clinical Pathophysiology, Endocrine Unit (M.M., L.I., C.P., M.S.), Respiratory Pathophysiology Unit (W.C.), and the Institute of Internal Medicine, Cardiovascular Unit (C.L., G.L.V., F.F.), University of Florence, and the Cardiovascular Ultrasound Unit (G.B.), Azienda Ospedaliera Careggi, Florence, Italy.

Correspondence to Massimo Mannelli, MD, Dept of Clinical Pathophysiology, Endocrine Unit, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. E-mail m.mannelli{at}dfc.unifi.it

Abstract—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 ß2 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.

Key Words: dopamine • plasma • norepinephrine • heart

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