title: Hormonal influences on cardiovascular norepinephrine transporter responses in healthy women.
abstract: 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.
authors.affiliation: Medical University Charité, Franz Volhard Clinical Research Center, Helios Klinikum Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Iryna
authors.initials: I
authors.lastname: Moldovanova
authors.forename: Christoph
authors.initials: C
authors.lastname: Schroeder
authors.forename: Giris
authors.initials: G
authors.lastname: Jacob
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
authors.forename: Andre
authors.initials: A
authors.lastname: Diedrich
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Jens
authors.initials: J
authors.lastname: Jordan
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage*; D000328:Adult; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004967:Estrogens / Q000097:blood*; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D018737:Hand Strength; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007537:Isometric Contraction; D008183:Luteal Phase / Q000502:physiology; D009025:Morpholines / Q000008:administration & dosage*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism*; D011374:Progesterone / Q000097:blood*; D000077593:Reboxetine; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D004967:Estrogens; D009025:Morpholines; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human; D011374:Progesterone; D000077593:Reboxetine