Carey R M, Thorner M O, Ortt E M
J Clin Invest. 1980 Jul;66(1):10-8. doi: 10.1172/JCI109822.
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.
本研究旨在探讨多巴胺能机制在人体醛固酮分泌调控中的作用。五名正常男性受试者，在每日摄入150毫当量钠和60毫当量钾的恒定摄入量下处于代谢平衡状态，连续两天静脉注射10毫克特定多巴胺拮抗剂甲氧氯普胺。第一天，受试者在甲氧氯普胺给药前60分钟至给药后60分钟接受5%葡萄糖溶液（溶媒）输注；第二天，用每分钟4微克/千克的多巴胺输注替代溶媒。在溶媒存在下，甲氧氯普胺使血浆醛固酮浓度从2.4±1.1升高至最高17.2±2.8纳克/100毫升（P<0.01），血清催乳素浓度从7.5±5.0升高至最高82.2±8.7纳克/毫升（P<0.01）。每分钟4微克/千克的多巴胺未改变基础血浆醛固酮浓度，但显著减弱了醛固酮对甲氧氯普胺的反应；在多巴胺存在下，甲氧氯普胺使血浆醛固酮浓度从3.1±0.5升高至6.2±1.4纳克/100毫升（P<0.05）。与溶媒相比，多巴胺存在时甲氧氯普胺引起的醛固酮增量反应显著降低。每分钟4微克/千克的多巴胺将基础催乳素抑制至<3纳克/毫升，并抑制了催乳素对甲氧氯普胺的反应；在多巴胺存在下，甲氧氯普胺使血清催乳素浓度最高升高至8.5±2.3纳克/毫升。除了用每分钟2微克/千克的多巴胺代替每分钟4微克/千克的剂量进行研究外，对受试者采用相同方式进行研究。每分钟2微克/千克的多巴胺减弱了醛固酮和催乳素对甲氧氯普胺的反应，但效果不如每分钟4微克/千克的多巴胺剂量。在研究前下午6点、午夜和凌晨6点，对另外五名受试者分别用2.5毫克多巴胺激动剂溴隐亭或安慰剂预处理后，静脉注射10毫克甲氧氯普胺。溴隐亭抑制基础血清催乳素水平，并完全抑制催乳素对甲氧氯普胺的反应。相比之下，溴隐亭未改变基础血浆醛固酮浓度或醛固酮对甲氧氯普胺的反应。甲氧氯普胺、多巴胺或溴隐亭对血浆肾素活性、血浆皮质醇和血清钾浓度无影响。本研究结果表明，醛固酮对甲氧氯普胺的反应是由甲氧氯普胺在多巴胺受体水平的拮抗活性介导的。结果还进一步提示了对多巴胺激动剂多巴胺和溴隐亭反应的解离，并表明一种新型多巴胺受体可能抑制醛固酮分泌。
