A B S T R A C T This study was designed to investigate the possible role of dopaminergic mechanisms in the control ofthe 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 nglml (P < 0.001) within 15 min of its administration. At 1 h, plasma aldosterone and prolactin concentrationis 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 miim 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 ngIl00 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+. 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. INTRODUCTION Dopamine, a precursor of the sympathetic neurotransmitter norepinephrine, may itself be a major transmitter of the peripheral autonomic nervous system (1). The adrenergic component of this system is important in controlling renin release (2, 3), but little is known concerning the role of dopamine in the regulation of the renin-angiotensin-aldosterone system. Cuche et al. (4) have shown in man that the increase in plasma renin activity with upright posture is associated with a decrease in urinary dopamine and an increase in norepinephrine and epinephrine excretion. Alexander and colleagues (5) have reported that sodium-depleted subjects respond to dietary or intravenous sodium loading with an increase in urinary dopamine and a decrease in urinary norepinephrine. Thus, maneuvers which would be expected to alter the activity of the renin-angiotensin-aldosterone system are ass...

This study was designed to investigate the role of dopaminergic mechanisms in the control of aldosterone secretion in man. Five normal male subjects in metabolic balance at 150 meq sodium/d and 60 meq potassium/d constant intake received the specific dopamine antagonist, metoclopramide, 10 mg i.v. on 2 consecutive d. On the 1st d, the subjects received an infusion of 5% glucose solution (vehicle) from 60 min before to 60 min after metoclopramide administration; on the 2nd d, an infusion of dopamine 4 mug/kg per min was substituted for vehicle. Metoclopramide in the presence of vehicle increased plasma aldosterone concentrations from 2.4+/-1.1 to a maximum of 17.2+/-2.8 ng/100 ml (P < 0.01) and serum prolactin concentrations from 7.5+/-5.0 to a maximum of 82.2+/-8.7 ng/ml (P < 0.01). Dopamine 4 mug/kg per min did not alter basal plasma aldosterone concentrations, but blunted the aldosterone responses to metoclopramide significantly; in the presence of dopamine, plasma aldosterone concentrations increased from 3.1+/-0.5 to 6.2+/-1.4 ng/100 ml (P < 0.05) in response to metoclopramide. The incremental aldosterone responses to metoclopramide were significantly lower in the presence of dopamine than with vehicle. Dopamine 4 mug/kg per min suppressed basal prolactin to <3 ng/ml and inhibited the prolactin responses to metoclopramide; serum prolactin concentrations increased to a maximum of 8.5+/-2.3 ng/ml with metoclopramide in the presence of dopamine. The subjects were studied in the same manner except that dopamine 2 mug/kg per min was administered instead of the 4-mug/kg per min dose. Dopamine 2 mug/kg per min attenuated the aldosterone and prolactin responses to metoclopramide, but was less effective than the 4-mug/kg per min dose of dopamine. Metoclopramide 10 mg i.v. was administered to five additional subjects after pretreatment with the dopamine agonist, bromocriptine, 2.5 mg or placebo at 6 p.m., midnight, and 6 a.m. before study. Bromocriptine suppressed basal serum prolactin levels and completely inhibited the prolactin responses to metoclopramide. In contrast, bromocriptine did not alter basal plasma aldosterone concentrations or the aldosterone responses to metoclopramide. Plasma renin activity, plasma cortisol, and serum potassium concentrations were unchanged by metoclopramide, dopamine, or bromocriptine. The results of this study suggest that the aldosterone response to metoclopramide is mediated by metoclopramide's antagonist activity at the dopamine receptor level. The results further suggest dissociation of the responses to the dopamine agonists, dopamine and bromocriptine, and indicate that a new type of dopamine receptor may inhibit aldosterone secretion.

This study was designed to investigate the influence of dietary sodium restriction on plasma and urine dopamine levels. Five normal white male volunteer subjects wee studied in metabolic balance at constant 150 meq sodium, 60 meq potassium intake and then daily for 7 days on an isocaloric constant diet of 10 meq sodium and 60 meq potassium/day. With dietary sodium restriction, urinary sodium excretion decreased from 152 +/- 13 meq/day in stepwise fashion to 7 +/- 1 meq/day (P less than 0.001) on day 7. On the first day of dietary sodium restriction, a sodium deficit of 122 meq was associated with a decrease in supine plasma dopamine concentration from 58 +/- 10 to 45 +/- 7 pg/ml (P less than values for 2 days but decreased again to 43 +/- 12 pg/ml (P less than 0.05) on day 4 of sodium restriction and remained significantly lower than control on days 5-7 of sodium restriction (P less than 0.01). Supine plasma norepinephrine concentration increased from 193 +/- 34 to 232 +/- 29 pg/ml (P less than 0.05) on day 1 of sodium restriction and remained elevated during each subsequent day of low sodium intake (P less than 0.001). Supine plasma epinephrine concentration was unchanged by sodium restriction. Urinary dopamine excretion decreased from 12 +/- 2 to 8 +/- 1 microgram/h (P less than 0.05) on day 2 of sodium restriction and remained significantly low during each subsequent day of low sodium intake. Urinary norepinephrine was unchanged by sodium restriction. The data indicate a variable decrease in plasma dopamine concentration and a constant decrease in urinary dopamine excretion during the course of dietary sodium restriction in man.

gested that the pressor response to angiotensin II (All) is diminished in the immature organism compared to the adult organism.