Schroeder Christoph, Adams Frauke, Boschmann Michael, Tank Jens, Haertter Sebastian, Diedrich Andre, Biaggioni Italo, Luft Friedrich C, Jordan Jens
Franz Volhard Clinical Research Center, Haus 129, Medical Faculty of the Charité-Campus Buch, Wiltbergstrasse 50, 13125 Berlin, Germany.
Am J Physiol Regul Integr Comp Physiol. 2004 May;286(5):R851-6. doi: 10.1152/ajpregu.00689.2003. Epub 2004 Jan 15.
Norepinephrine transporter (NET) function has a central role in the regulation of synaptic norepinephrine concentrations. Clinical observations in orthostatic intolerance patients suggest a gender difference in NET function. We compared the cardiovascular response to selective NET inhibition with reboxetine between 12 healthy men and 12 age-matched women. Finger blood pressure, brachial blood pressure, and heart rate were measured. The subjects underwent cardiovascular autonomic reflex testing and a graded head-up tilt test. In a separate study, we applied incremental concentrations of tyramine and isoproterenol through subcutaneous microdialysis catheters in eight men and in eight women. NET inhibition elicited a threefold greater increase in supine blood pressure in men than women (P < 0.05). The pressor response was driven by an increased cardiac output. The orthostatic heart rate increase during NET inhibition was greater in men than women (56 +/- 5 beats/min in men, 42 +/- 4 beats/min in women, P < 0.001). In contrast, NET inhibition resulted in a similar suppression in the cold pressor and handgrip response, low-frequency blood pressure oscillations, and venous norepinephrine in the supine position. Men and women were similarly sensitive to the lipolytic effect of isoproterenol and tyramine. We conclude that NET inhibition results in more pronounced changes in cardiac regulation in men than women. Our observations suggest that the NET contribution to cardiac norepinephrine turnover may be decreased in women. The gender difference in NET function may not be expressed in tissues that are less NET dependent than the heart.
去甲肾上腺素转运体（NET）功能在调节突触去甲肾上腺素浓度方面起着核心作用。体位性不耐受患者的临床观察表明，NET功能存在性别差异。我们比较了12名健康男性和12名年龄匹配女性在使用瑞波西汀选择性抑制NET后的心血管反应。测量了手指血压、肱动脉血压和心率。受试者接受了心血管自主反射测试和分级头高位倾斜试验。在另一项研究中，我们通过皮下微透析导管对8名男性和8名女性应用递增浓度的酪胺和异丙肾上腺素。抑制NET后，男性仰卧位血压升高幅度比女性大3倍（P<0.05）。升压反应是由心输出量增加驱动的。抑制NET期间，男性直立位心率增加幅度大于女性（男性为56±5次/分钟，女性为42±4次/分钟，P<0.001）。相比之下，抑制NET对冷加压和握力反应、低频血压振荡以及仰卧位静脉去甲肾上腺素的抑制作用相似。男性和女性对异丙肾上腺素和酪胺的脂解作用同样敏感。我们得出结论，与女性相比，抑制NET对男性心脏调节的影响更为显著。我们的观察结果表明，女性心脏中NET对去甲肾上腺素周转的贡献可能降低。NET功能的性别差异可能在比心脏对NET依赖性更低的组织中未表现出来。
