title: Mechanisms contributing to low orthostatic tolerance in women: the influence of oestradiol.
abstract: The impact of 17β-oestradiol (E2) exposure on autonomic control of orthostasis in young women is unclear. We tested the hypothesis that autonomic cardiovascular regulation is more sensitive to E2 exposure in women with low orthostatic tolerance. Women underwent an initial maximal lower body negative pressure (LBNP) test to place them into a low (LT, n = 7, 22 ± 1 years old, body mass index 22 ± 1 kg m(-2)) or a high orthostatic tolerance group (HT, n = 7, 22 ± 1 years old, body mass index 24 ± 1 kg m(-2)). We then suppressed endogenous reproductive hormone production using a gonadotrophin-releasing hormone antagonist (GnRHant) for 10 days, with E2 administration during the last 7 days of GnRHant. We measured R-R interval and beat-by-beat blood pressure during the modified Oxford protocol, and changes in heart rate, blood pressure and forearm vascular resistance (FVR) during submaximal LBNP. During submaximal LBNP, FVR increased in HT (ANOVA P < 0.05) but not in LT (ANOVA P > 0.05), and stroke volume was lower in LT relative to HT at all levels of LBNP (P < 0.05). Compared with GnRHant, E2 administration shifted FVR lower in LT (ANOVA P < 0.05), with no effect in HT. Administration of E2 increased baroreflex control of heart rate (derived from the modified Oxford protocol) in LT (GnRHant 10.7 ± 2.5 ms mmHg(-1) vs. E2 16.1 ± 2.4 ms mmHg(-1), P < 0.05) but not in HT (GnRHant 13.4 ± 1.9 ms mmHg(-1) vs. E2 15.3 ± 2.4 ms mmHg(-1), n.s.). In conclusion, blunted peripheral vasoconstriction and lower stroke volume contribute to compromised orthostatic tolerance in women; this inability to vasoconstrict is further exacerbated by exposure to E2. Furthermore, E2 administration increases baroreflex-mediated heart rate responses to orthostasis in low orthostatic tolerant women, which is likely to be a compensatory mechanism for the blunted peripheral vascular resistance and lower central volume.
authors: Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE 19716, USA. mwenner@udel.edu
authors: Megan M
authors: MM
authors: Wenner
authors: Ala' S
authors: AS
authors: Haddadin
authors: Hugh S
authors: HS
authors: Taylor
authors: Nina S
authors: NS
authors: Stachenfeld
mesh_terms: D000328:Adult; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D004244:Dizziness / Q000503:physiopathology; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D013318:Stroke Volume; D055815:Young Adult
chemical_list: D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; C061018:ganirelix
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