Schmidt B M, Georgens A C, Martin N, Tillmann H C, Feuring M, Christ M, Wehling M
Institute of Clinical Pharmacology, University Hospital of Mannheim, Faculty for Clinical Medicine Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
J Clin Endocrinol Metab. 2001 Feb;86(2):761-7. doi: 10.1210/jcem.86.2.7259.
Interactions between the renin-angiotensin-aldosterone system and the adrenergic system are complex and have mainly been attributed to angiotensin II, with knowledge about aldosterone action much less advanced. Only recently has evidence been forthcoming that aldosterone blunts the baroreceptor reflex and lowers heart rate variability in humans. Both effects point to an adrenergic-like action of aldosterone. It has been proposed that this blunting of baroreceptor sensitivity is mediated nongenomically and that nongenomic aldosterone action itself is modulated by the adrenergic system. The aim of the present study was to prove the hypothesis of an interaction between the autonomic nervous system and rapid, nongenomic aldosterone effects. We conducted a randomized, double blind, 8-fold cross-over trial on 18 healthy male volunteers. After pretreatment with the beta-blocking agent esmolol, the beta-agonist dobutamine, the alpha(1)-agonist phenylephrine, or placebo, placebo (0.9% NaCl) or aldosterone (0.5 mg) was injected. After aldosterone injection the peak plasma levels were supraphysiological, reaching nanomolar concentrations. Primary target variables were differences in changes in mean arterial blood pressure, systemic vascular resistance, and cardiac output depending on the pretreatment. Cardiovascular parameters were measured by impedance cardiography during the maintained infusion of the adrenergic modulators for 45 min. Comparing pretreatments, diverse acute, and thus nongenomic, effects of aldosterone on mean arterial blood pressure were observed. After esmolol pretreatment, aldosterone caused an increase in mean arterial blood pressure by 4.1%, whereas after dobutamine pretreatment mean arterial blood pressure decreased by 1.6%, and the difference was statistically significant (P < 0.01). These effects were significant (P < 0.005) for the first 12 min, underlining their nongenomic nature. Our data support the hypothesis that aldosterone, via nongenomic mechanisms, has diverse effects on the cardiovascular system that depend on the preexisting adrenergic state. Furthermore, aldosterone blunts the blood pressure-lowering effect of the beta-blocking agent esmolol by a nongenomic mechanism.
肾素-血管紧张素-醛固酮系统与肾上腺素能系统之间的相互作用十分复杂，且主要归因于血管紧张素II，而关于醛固酮作用的了解则相对较少。直到最近才有证据表明，醛固酮会减弱人体的压力感受器反射并降低心率变异性。这两种效应均表明醛固酮具有类似肾上腺素能的作用。有人提出，压力感受器敏感性的这种减弱是通过非基因组介导的，并且非基因组醛固酮作用本身受肾上腺素能系统调节。本研究的目的是验证自主神经系统与快速、非基因组醛固酮效应之间存在相互作用这一假设。我们对18名健康男性志愿者进行了一项随机、双盲、8次交叉试验。在用β受体阻滞剂艾司洛尔、β受体激动剂多巴酚丁胺、α(1)受体激动剂去氧肾上腺素或安慰剂进行预处理后，注射安慰剂（0.9%氯化钠）或醛固酮（0.5毫克）。注射醛固酮后，血浆峰值水平超过生理水平，达到纳摩尔浓度。主要目标变量是根据预处理情况，平均动脉血压、全身血管阻力和心输出量变化的差异。在持续输注肾上腺素能调节剂45分钟期间，通过阻抗心动图测量心血管参数。比较预处理情况时，观察到醛固酮对平均动脉血压有不同的急性（即非基因组）效应。用艾司洛尔预处理后，醛固酮使平均动脉血压升高4.1%，而用多巴酚丁胺预处理后，平均动脉血压下降1.6%，差异具有统计学意义（P<0.01）。这些效应在最初12分钟内具有显著性（P<0.005），突出了它们的非基因组性质。我们的数据支持这样的假设，即醛固酮通过非基因组机制，对心血管系统具有不同的效应，这取决于预先存在的肾上腺素能状态。此外，醛固酮通过非基因组机制减弱β受体阻滞剂艾司洛尔的降压作用。
