Published online before print February 7, 2008, doi: 10.1161/HYPERTENSIONAHA.107.107433
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(Hypertension. 2008;51:1203.)
© 2008 American Heart Association, Inc.
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Hormonal Influences on Cardiovascular Norepinephrine Transporter Responses in Healthy Women
From the Medical University Charité (I.M., C.S., F.C.L., J.J.), Franz Volhard Clinical Research Center, Helios Klinikum Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany; Jacob Recanati Autonomic Dysfunction Center (G.J.), Rambam Medical Center, Haifa, Israel; Department for Psychiatry (C.H.), University Mainz, Mainz, Germany; and the Autonomic Dysfunction Service (A.D.), Vanderbilt University, Nashville, Tenn.
Correspondence to Jens Jordan, Franz Volhard Clinical Research Center, Haus 129, Medical University Charité, Campus Buch, Wiltbergstr 50, 13125 Berlin, Germany. E-mail jens.jordan{at}charite.de
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.
Key Words: menstrual cycle • female sex hormones • norepinephrine transporter • cardiovascular regulation • human