title: Discordant orthostatic reflex renin-angiotensin and sympathoneural responses in premenopausal exercising-hypoestrogenic women.
abstract: Our prior observations in normotensive postmenopausal women stimulated the hypotheses that compared with eumenorrheic women, active hypoestrogenic premenopausal women with functional hypothalamic amenorrhea would demonstrate attenuated reflex renin-angiotensin-aldosterone system responses to an orthostatic challenge, whereas to defend blood pressure reflex increases in muscle, sympathetic nerve activity would be augmented. To test these hypotheses, we assessed, in recreationally active women, 12 with amenorrhea (ExFHA; aged 25 ± 1 years; body mass index 20.7 ± 0.7 kg/m(2); mean ± SEM) and 17 with eumenorrhea (ExOv; 24 ± 1 years; 20.9 ± 0.5 kg/m(2)), blood pressure, heart rate, plasma renin, angiotensin II, aldosterone, and muscle sympathetic nerve activity at supine rest and during graded lower body negative pressure (-10, -20, and -40 mm Hg). At baseline, heart rate and systolic blood pressure were lower (P<0.05) in ExFHA (47 ± 2 beats/min and 94 ± 2 mm Hg) compared with ExOv (56 ± 2 beats/min and 105 ± 2 mm Hg), but muscle sympathetic nerve activity and renin-angiotensin-aldosterone system constituents were similar (P>0.05). In response to graded lower body negative pressure, heart rate increased (P<0.05) and systolic blood pressure decreased (P<0.05) in both groups, but these remained consistently lower in ExFHA (P<0.05). Lower body negative pressure elicited increases (P<0.05) in renin, angiotensin II, and aldosterone in ExOv, but not in ExFHA (P>0.05). Muscle sympathetic nerve activity burst incidence increased reflexively in both groups, but more so in ExFHA (P<0.05). Otherwise, healthy hypoestrogenic ExFHA women demonstrate low blood pressure and disruption of the normal circulatory response to an orthostatic challenge: plasma renin, angiotensin II, and aldosterone fail to increase and blood pressure is defended by an augmented sympathetic vasoconstrictor response.
authors.affiliation: From the Cardiovascular Research Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada (E.O'D., J.M.G.); and Department of Medicine, Division of Cardiology, University Health Network at Mount Sinai Hospital (J.M.G., S.M., H.M., B.L.M, J.S.F.), and Department of Medicine, Division of Cardiology at the Women's College Hospital (P.J.H.), University of Toronto, Ontario, Canada.
authors.forename: Emma
authors.initials: E
authors.lastname: O'Donnell
authors.affiliation: From the Cardiovascular Research Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada (E.O'D., J.M.G.); and Department of Medicine, Division of Cardiology, University Health Network at Mount Sinai Hospital (J.M.G., S.M., H.M., B.L.M, J.S.F.), and Department of Medicine, Division of Cardiology at the Women's College Hospital (P.J.H.), University of Toronto, Ontario, Canada.
authors.forename: Jack M
authors.initials: JM
authors.lastname: Goodman
authors.affiliation: From the Cardiovascular Research Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada (E.O'D., J.M.G.); and Department of Medicine, Division of Cardiology, University Health Network at Mount Sinai Hospital (J.M.G., S.M., H.M., B.L.M, J.S.F.), and Department of Medicine, Division of Cardiology at the Women's College Hospital (P.J.H.), University of Toronto, Ontario, Canada.
authors.forename: Susanna
authors.initials: S
authors.lastname: Mak
authors.affiliation: From the Cardiovascular Research Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada (E.O'D., J.M.G.); and Department of Medicine, Division of Cardiology, University Health Network at Mount Sinai Hospital (J.M.G., S.M., H.M., B.L.M, J.S.F.), and Department of Medicine, Division of Cardiology at the Women's College Hospital (P.J.H.), University of Toronto, Ontario, Canada.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Murai
authors.affiliation: From the Cardiovascular Research Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada (E.O'D., J.M.G.); and Department of Medicine, Division of Cardiology, University Health Network at Mount Sinai Hospital (J.M.G., S.M., H.M., B.L.M, J.S.F.), and Department of Medicine, Division of Cardiology at the Women's College Hospital (P.J.H.), University of Toronto, Ontario, Canada.
authors.forename: Beverley L
authors.initials: BL
authors.lastname: Morris
authors.affiliation: From the Cardiovascular Research Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada (E.O'D., J.M.G.); and Department of Medicine, Division of Cardiology, University Health Network at Mount Sinai Hospital (J.M.G., S.M., H.M., B.L.M, J.S.F.), and Department of Medicine, Division of Cardiology at the Women's College Hospital (P.J.H.), University of Toronto, Ontario, Canada.
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
authors.affiliation: From the Cardiovascular Research Laboratory, Department of Exercise Sciences, University of Toronto, Toronto, Ontario, Canada (E.O'D., J.M.G.); and Department of Medicine, Division of Cardiology, University Health Network at Mount Sinai Hospital (J.M.G., S.M., H.M., B.L.M, J.S.F.), and Department of Medicine, Division of Cardiology at the Women's College Hospital (P.J.H.), University of Toronto, Ontario, Canada. Paula.harvey@wchospital.ca.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Harvey
mesh_terms: D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D004967:Estrogens / Q000097:blood / Q000172:deficiency*; D015444:Exercise / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D011187:Posture / Q000502:physiology*; D017697:Premenopause / Q000502:physiology*; D012016:Reference Values; D012018:Reflex / Q000502:physiology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D055815:Young Adult
chemical_list: D004967:Estrogens; D000804:Angiotensin II; D000450:Aldosterone; D012083:Renin
keywords: blood pressure; estrogens; exercise; renin–angiotensin system; sympathetic nervous system