MSNA_Manuscript_Hypertension_Jan 6, 2015_ACCEPTED.pdf (372.33 kB)

Discordant orthostatic reflex renin-angiotensin and sympathoneural responses in premenopausal exercising-hypoestrogenic women

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journal contribution
posted on 17.03.2016 by Emma ODonnell, Jack M. Goodman, Susanna Mak, Hisayoshi Murai, Beverley L. Morris, John S. Floras, Paula J. Harvey
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.


PJH was funded by a Pfizer Cardiovascular Independent Research Award (NRA 3840028). JSF holds the Canada Research Chair in Integrative Cardiovascular Biology. EOD received doctoral funding from the Canadian Institute of Health Research. HM was supported by the Bluma Appel International Fellowship of Mount Sinai Hospital. BLM was supported by an operating grant from the Heart and Stroke Foundation on Ontario.



  • Sport, Exercise and Health Sciences

Published in







1089 - 1095


O'DONNELL, E. ... et al., 2015. Discordant orthostatic reflex renin-angiotensin and sympathoneural responses in premenopausal exercising-hypoestrogenic women. Hypertension, 65 (5), pp. 1089 - 1095.


© American Heart Association, Inc.


AM (Accepted Manuscript)

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This article was accepted for publication in the journal Hypertension [© American Heart Association] and the definitive version is available at: