Suppression of basal and stimulated noradrenergic activities by the dopamine agonist bromocriptine in man

This study was designed to determine the effects of dopaminergic receptor stimulation on basal and stimulated catecholamine release in man. Five normal white male volunteer subjects were studied in metabolic balance at constant 150-meq sodium, 60-meq potassium intake and then daily for 8 days on an isocaloric constant diet of 10 meq sodium and 60 meq potassium/day in each of two separate protocols. In one protocol, the subjects received the dopamine agonist bromocriptine for 14 days before and during the study; in the other protocol, placebo was substituted for bromocriptine. During normal sodium intake, bromocriptine suppressed supine plasma norepinephrine concentrations from 193 +/- 10 to 159 +/- 9 pg/ml (P = 0.01). Dietary sodium depletion increased supine plasma norepinephrine concentrations in subjects taking placebo from 193 +/- 10 to 229 +/- 10 pg/ml (P less than 0.001). Bromocriptine prevented the supine plasma norepinephrine response to sodium depletion. After discontinuation of bromocriptine treatment, supine plasma norepinephrine concentrations returned to placebo control values. Upright posture stimulated an increase in plasma norepinephrine concentrations from 193 +/- 10 to 419 +/- 30 pg/ml (P = 0.0001) during normal sodium intake, and bromocriptine suppressed this response from 419 +/- 30 to 286 +/- 29 pg/ml (P = 0.004). Dietary sodium depletion enhanced the plasma norepinephrine response to upright posture, and bromocriptine markedly suppressed this enhancement. After discontinuation of bromocriptine treatment, supine and upright plasma norepinephrine concentrations returned to placebo control values. Bromocriptine induced a parallel downward shift in the inverse hyperbolic relationship between the plasma norepinephrine concentration and urinary sodium excretion in erect subjects, and decreased overnight urinary norepinephrine excretion in supine subjects from 1.1 +/- 0.1 to 0.6 +/- 0.1 ng/h (P = 0.0002). No consistent effects of bromocriptine on plasma epinephrine or dopamine concentrations were observed. The results of this study strongly suggest an inhibitory action of dopamine receptor stimulation by bromocriptine on basal and stimulated norepinephrine output at noradrenergic nerve terminals in the central nervous system and/or the periphery.