Perinatal growth restriction (GR) is associated with heightened sympathetic tone and hypertension. We have previously shown that naturally occurring neonatal GR programmes hypertension in male but not female mice. We therefore hypothesized that intact ovarian function or post-ovariectomy (OVX) oestrogen administration protects GR female mice from hypertension. Utilizing a non-interventional model that categorizes mice with weanling weights below the tenth percentile as GR, control and GR adult mice were studied at three distinct time points: baseline, post-OVX and post-OVX with oral oestrogen replacement. OVX elicited hypertension in GR mice that was significantly exacerbated by psychomotor arousal (systolic blood pressure at light to dark transition: control 122±2; GR 119±2; control-OVX 116±3; GR-OVX 126±3 mmHg). Oestrogen partially normalized the rising blood pressure surge seen in GR-OVX mice (23±7% reduction). GR mice had left ventricular hypertrophy, and GR-OVX mice in particular had exaggerated bradycardic responses to sympathetic blockade. For GR mice, a baseline increase in baroreceptor reflex sensitivity and high frequency spectral power support a vagal compensatory mechanism, and that compensation was lost following OVX. For GR mice, the OVX-induced parasympathetic withdrawal was partially restored by oestrogen (40±25% increase in high frequency spectral power, P<0.05). In conclusion, GR alters cardiac morphology and cardiovascular regulation. The haemodynamic consequences of GR are attenuated in ovarian-sufficient or oestrogen-replete females. Further investigations are needed to define the role of hormone replacement therapy targeted towards young women with oestrogen deficiency and additional cardiovascular risk factors, including perinatal GR, cardiac hypertrophy and morning surge hypertension.
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Radiation nephropathy is mitigated by EET-A and also by captopril. The severe histological injury of radiation nephropathy includes cast formation and mesangiolysis. Both are significantly attenuated by EET-A or captopril. PAS stained kidney, 200x magnification. For further details see pp. 587–599. Image kindly provided by Dr. Md Abdul Hye Khan.
Research Article|
March 08 2016
Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice
Sarah E. Haskell;
Sarah E. Haskell
*Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Veronica Peotta;
Veronica Peotta
*Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Benjamin E. Reinking;
Benjamin E. Reinking
*Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Catherine Zhang;
Catherine Zhang
*Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Vivian Zhu;
Vivian Zhu
*Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Elizabeth J. Kenkel;
Elizabeth J. Kenkel
*Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
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Robert D. Roghair
*Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
Correspondence: Dr Robert D. Roghair (email robert-roghair@uiowa.edu).
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Publisher: Portland Press Ltd
Received:
September 30 2015
Revision Received:
January 05 2016
Accepted:
January 21 2016
Accepted Manuscript online:
January 21 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (8): 613–623.
Article history
Received:
September 30 2015
Revision Received:
January 05 2016
Accepted:
January 21 2016
Accepted Manuscript online:
January 21 2016
Citation
Sarah E. Haskell, Veronica Peotta, Benjamin E. Reinking, Catherine Zhang, Vivian Zhu, Elizabeth J. Kenkel, Robert D. Roghair; Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice. Clin Sci (Lond) 1 April 2016; 130 (8): 613–623. doi: https://doi.org/10.1042/CS20150693
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