McKenna T J, Island D P, Nicholson W E, Liddle G W
J Clin Invest. 1979 Jul;64(1):287-91. doi: 10.1172/JCI109450.
The possibility that dopamine may play a role in the in vivo control of aldosterone production in man was suggested to us by reports from others; (a) that bromocriptine, a dopaminergic agonist, inhibits the aldosterone response to diuresis and to the infusion of angiotensin or ACTH; and (b) that metaclopramide, a dopamine blocking agent, causes elevations in plasma aldosterone levels. To determine whether such effects were direct or indirect, we examined the action of dopamine on aldosterone biosynthesis in isolated, bovine adrenal cells. Dopamine significantly inhibits the aldosterone response to angiotensin (P < 0.001), but does not influence basal aldosterone biosynthesis. It has previously been reported that angiotensin stimulates both the early and late phases of aldosterone biosynthesis. The present experiments demonstrated that the enhancing effect of angiotensin on the conversion of deoxycorticosterone to aldosterone (late phase of aldosterone biosynthesis) was almost completely inhibited by dopamine (P < 0.001). A significant inhibitory effect of dopamine (10 nM) was seen even when aldosterone biosynthesis was stimulated by a grossly supraphysiological concentration of angiotensin II (10 muM). However, these studies did not demonstrate any direct effect of dopamine on the early phase of aldosterone biosynthesis (cholesterol to pregnenolone) basally or when stimulated, or on the late phase of aldosterone biosynthesis under basal conditions. These in vitro studies suggest a direct inhibitory role for dopamine on the late phase of aldosterone biosynthesis, which may account for the in vivo inhibition of the aldosterone response to angiotensin in subjects treated with a dopaminergic agent.
其他人的报告向我们提示，多巴胺可能在人体内醛固酮分泌的体内调节中发挥作用；(a) 多巴胺能激动剂溴隐亭可抑制醛固酮对利尿以及对输注血管紧张素或促肾上腺皮质激素的反应；(b) 多巴胺阻滞剂甲氧氯普胺可使血浆醛固酮水平升高。为了确定这些作用是直接的还是间接的，我们研究了多巴胺对分离的牛肾上腺细胞中醛固酮生物合成的作用。多巴胺可显著抑制醛固酮对血管紧张素的反应（P < 0.001），但不影响基础醛固酮生物合成。此前有报道称，血管紧张素可刺激醛固酮生物合成的早期和晚期阶段。本实验表明，多巴胺几乎完全抑制了血管紧张素对脱氧皮质酮转化为醛固酮的增强作用（醛固酮生物合成的晚期阶段）（P < 0.001）。即使醛固酮生物合成受到超生理浓度的血管紧张素 II（10 μM）刺激，多巴胺（10 nM）仍有显著抑制作用。然而，这些研究并未证明多巴胺在基础状态下或受到刺激时对醛固酮生物合成早期阶段（胆固醇转化为孕烯醇酮）有任何直接作用，也未证明在基础条件下对醛固酮生物合成晚期阶段有直接作用。这些体外研究表明，多巴胺对醛固酮生物合成的晚期阶段具有直接抑制作用，这可能解释了在用多巴胺能药物治疗的受试者中，醛固酮对血管紧张素的反应在体内受到抑制的现象。
