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甲氧氯普胺和多巴胺对正常人和恒河猴(猕猴)血浆醛固酮浓度的影响:一种研究多巴胺对醛固酮分泌控制的新模型。

The effect of metoclopramide and dopamine on plasma aldosterone concentration in normal man and rhesus monkeys (Macaca mulatta): a new model to study dopamine control of aldosterone secretion.

作者信息

Brown R D, Billman G E, Kem D C, Stone H L, Jiang N S, Kao P, Hegstad R L

出版信息

J Clin Endocrinol Metab. 1982 Nov;55(5):828-32. doi: 10.1210/jcem-55-5-828.

Abstract

Metoclopramide, a dopamine receptor antagonist, increases plasma aldosterone concentration in man, suggesting that dopamine regulates the secretion of aldosterone. In the current study, we administered metoclopramide to rhesus monkeys and normal subjects and compared the time-course and dose-response characteristics of plasma aldosterone. We also examined the effect of dopamine on the plasma aldosterone response to metoclopramide in both species. Six male rhesus monkeys and several normal subjects (five women and two men) were studied on diets providing an estimated daily sodium intake of 70 mg/kg. In both species the peak increase in plasma aldosterone occurred 15 min after metoclopramide was injected. The peak plasma aldosterone value was 3-fold higher than control values. There were no significant changes in PRA, cortisol or potassium, whereas plasma PRL increased 7-fold in the monkeys and 11-fold in the normal subjects. After 0.04 mg/kg metoclopramide, there was no change in plasma aldosterone concentration in the monkeys, whereas aldosterone increased significantly (delta = 3.7 +/- 0.68 ng/dl) in the human subjects. The half-maximal dose of metoclopramide was also higher in the monkeys than in the normal subjects. A dopamine infusion at 4.0 to 8.0 micrograms/kg . min partially suppressed the plasma aldosterone response to metoclopramide in both the human subjects and the monkeys. This study demonstrates that metoclopramide produces dose-related increases in plasma aldosterone concentration in the nonhuman primate that are similar to those in normal man and that the increases can be inhibited by dopamine. We conclude that aldosterone secretion may be under dopamine control and that the rhesus monkey should be an excellent model in which to study further the regulation of aldosterone by dopamine.

摘要

甲氧氯普胺是一种多巴胺受体拮抗剂,可使人体血浆醛固酮浓度升高,这表明多巴胺对醛固酮的分泌具有调节作用。在本研究中,我们给恒河猴和正常受试者注射了甲氧氯普胺,并比较了血浆醛固酮的时程和剂量反应特征。我们还研究了多巴胺对这两个物种血浆醛固酮对甲氧氯普胺反应的影响。选取6只雄性恒河猴和若干正常受试者(5名女性和2名男性),给予他们每日钠摄入量估计为70 mg/kg的饮食。在这两个物种中,注射甲氧氯普胺后15分钟血浆醛固酮出现峰值升高。血浆醛固酮峰值比对照值高3倍。血浆肾素活性(PRA)、皮质醇或钾没有显著变化,而恒河猴的血浆催乳素(PRL)升高了7倍,正常受试者升高了11倍。注射0.04 mg/kg甲氧氯普胺后,恒河猴的血浆醛固酮浓度没有变化,而人类受试者的醛固酮显著升高(Δ = 3.7 ± 0.68 ng/dl)。恒河猴中产生半数最大效应的甲氧氯普胺剂量也高于正常受试者。以4.0至8.0微克/千克·分钟的速度输注多巴胺可部分抑制人类受试者和恒河猴血浆醛固酮对甲氧氯普胺的反应。本研究表明,甲氧氯普胺可使非人类灵长类动物的血浆醛固酮浓度产生与剂量相关的升高,这与正常人类相似,且这种升高可被多巴胺抑制。我们得出结论,醛固酮的分泌可能受多巴胺控制,恒河猴应是进一步研究多巴胺对醛固酮调节作用的理想模型。

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