Effects of Metoclopramide and Bromocriptine on the Renin-Angiotensin-Aldosterone System in Man: <i>DOPAMINERGIC CONTROL OF ALDOSTERONE</i>

Robert M. Carey; Michael O. Thorner; Elizabeth M. Ortt

doi:10.1172/JCI109356

Effects of Metoclopramide and Bromocriptine on the Renin-Angiotensin-Aldosterone System in Man: DOPAMINERGIC CONTROL OF ALDOSTERONE

Robert M. Carey, Michael O. Thorner, and Elizabeth M. Ortt

Published April 1, 1979 - More info

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Abstract

This study was designed to investigate the possible role of dopaminergic mechanisms in the control of the renin-angiotensin-aldosterone system in normal man. Six normal male subjects in metabolic balance at 150 meq sodium, 60 meq potassium constant intake received the specific dopamine antagonist, metoclopramide, 10 mg i.v. or placebo followed by angiotensin II infusion 1 h later on 2 consecutive days. Metoclopramide increased plasma aldosterone concentration from 8.2±2.2 to 21.0±3.3 ng/100 ml (P < 0.005) and plasma prolactin concentration from 18.0±4.0 to 91.7±4.0 ng/ml (P < 0.001) within 15 min of its administration. At 1 h, plasma aldosterone and prolactin concentrations remained elevated at 16.8±2.1 ng/100 ml (P < 0.01) and 86.8±15.9 ng/ml (P < 0.005), respectively. Angiotensin II at 2, 4, and 6 pmol/kg per min further increased plasma aldosterone concentration to 27.2±3.4, 31.9±5.7, and 36.0±6.7 ng/100 ml (P < 0.02), respectively. Placebo did not alter plasma aldosterone or prolactin concentrations, but angiotensin II increased plasma aldosterone concentration to 13.7±2.4, 19.0±1.9, and 23.3±3.2 ng/100 ml (P < 0.005). The increment of plasma aldosterone concentration in response to angiotensin II was similar after metoclopramide or placebo.

The six subjects also received the dopamine agonist, bromocriptine, 2.5 mg or placebo at 6 p.m., midnight, and 6 a.m. followed by angiotensin II infusion on 2 consecutive d. Bromocriptine suppressed prolactin to <3 ng/ml. After placebo, plasma aldosterone concentration increased from 5.2±1.4 to 12.3±1.7, 17.2±2.2, and 21.8±3.5 ng/100 ml (P < 0.01) and after bromocriptine from 7.2±1.0 to 14.7±3.0, 19.8±3.2, and 23.4±1.6 ng/100 ml (P < 0.001) with each respective angiotensin II dose. No difference in the response to angiotensin II after bromocriptine or placebo was observed. Plasma renin activity, free 11-hydroxycorticoid concentration, and serum potassium concentration were unchanged by metoclopramide or bromocriptine.

The results suggest that aldosterone production is under maximum tonic dopaminergic inhibition which can be overridden with stimulation by angiotensin II in normal man.