Moldovanova Iryna, Schroeder Christoph, Jacob Giris, Hiemke Christoph, Diedrich Andre, Luft Friedrich C, Jordan Jens
Medical University Charité, Franz Volhard Clinical Research Center, Helios Klinikum Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Hypertension. 2008 Apr;51(4):1203-9. doi: 10.1161/HYPERTENSIONAHA.107.107433. Epub 2008 Feb 7.
Gender differences in human cardiovascular norepinephrine transporter function may be mediated through female sex hormones. We studied 16 healthy eumenorrheic women (25+/-1 years) during the early follicular phase (day 5+/-0) and midluteal phase (day 22+/-0) of the menstrual cycle. In a randomized, crossover, double-blind fashion, subjects ingested 8 mg of the selective norepinephrine transporter inhibitor reboxetine or placebo. We monitored heart rate, blood pressure, and thoracic bioimpedance at rest and during standard autonomic function tests, including head-up tilt. Venous estradiol and progesterone concentrations were higher in the luteal than in the follicular phase but did not differ between placebo and norepinephrine transporter inhibition testing days. On placebo, hemodynamics at rest and in response to different stressors were mostly identical between cycle phases. In the supine position, norepinephrine transporter inhibition increased blood pressure and stroke volume to a greater extent during the follicular than during the luteal phase. Conversely, the increase in heart rate and cardiac output with norepinephrine transporter inhibition was augmented in the luteal compared with the follicular phase. During head-up tilt with norepinephrine transporter inhibition, blood pressure and stroke volume decreased to a greater extent in the follicular than in the luteal phase. The tachycardic response to head-up tilt with norepinephrine transporter inhibition was augmented in the follicular phase. Our study suggests that sex hormones alter the hemodynamic response to norepinephrine transporter inhibition in women. The phenomenon may be explained by an effect of female sex hormones on norepinephrine transporter function, on compensatory cardiovascular responses, or both.
人类心血管去甲肾上腺素转运体功能的性别差异可能由女性性激素介导。我们研究了16名月经周期正常的健康女性（25±1岁），分别在月经周期的卵泡早期（第5±0天）和黄体中期（第22±0天）。受试者以随机、交叉、双盲的方式摄入8毫克选择性去甲肾上腺素转运体抑制剂瑞波西汀或安慰剂。我们在静息状态以及包括头高位倾斜在内的标准自主神经功能测试期间监测心率、血压和胸段生物阻抗。黄体期的静脉雌二醇和孕酮浓度高于卵泡期，但在安慰剂组和去甲肾上腺素转运体抑制测试日之间没有差异。服用安慰剂时，静息状态下以及对不同应激源的血流动力学在不同周期阶段大多相同。在仰卧位，去甲肾上腺素转运体抑制在卵泡期比黄体期更大程度地升高血压和每搏输出量。相反，与卵泡期相比，黄体期去甲肾上腺素转运体抑制引起的心率和心输出量增加更为明显。在去甲肾上腺素转运体抑制状态下头高位倾斜时，卵泡期的血压和每搏输出量下降幅度比黄体期更大。去甲肾上腺素转运体抑制状态下头高位倾斜时的心动过速反应在卵泡期增强。我们的研究表明，性激素会改变女性对去甲肾上腺素转运体抑制的血流动力学反应。这种现象可能是由于女性性激素对去甲肾上腺素转运体功能、对代偿性心血管反应或两者的影响所致。
