Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice

Sarah E Haskell; Veronica Peotta; Benjamin E Reinking; Catherine Zhang; Vivian Zhu; Elizabeth J Kenkel; Robert D Roghair

doi:10.1042/CS20150693

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Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice

Journal article

Peer reviewed

Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice

Sarah E Haskell, Veronica Peotta, Benjamin E Reinking, Catherine Zhang, Vivian Zhu, Elizabeth J Kenkel and Robert D Roghair

Clinical science (1979), Vol.130(8), pp.613-623

04/2016

DOI: 10.1042/CS20150693

PMCID: PMC5036530

PMID: 26795436

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http://doi.org/10.1042/CS20150693View

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Abstract

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.

Adaptation, Physiological

Estrogen Replacement Therapy

Heart Rate

Body Weight

Ovariectomy

Administration, Oral

Mice, Inbred C57BL

Estradiol - administration & dosage

Cardiovascular System - innervation

Cardiovascular System - drug effects

Nicotinic Antagonists - pharmacology

Ganglionic Blockers - pharmacology

Circadian Rhythm

Motor Activity

Hypertension - physiopathology

Hypertension - etiology

Baroreflex - drug effects

Animals

Time Factors

Adrenergic alpha-1 Receptor Antagonists - pharmacology

Hypertension - prevention & control

Female

Blood Pressure - drug effects

Disease Models, Animal

Details

Title: Subtitle: Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice
Creators: Sarah E Haskell - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A
Veronica Peotta - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A
Benjamin E Reinking - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A
Catherine Zhang - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A
Vivian Zhu - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A
Elizabeth J Kenkel - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A
Robert D Roghair - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A. robert-roghair@uiowa.edu
Resource Type: Journal article
Publication Details: Clinical science (1979), Vol.130(8), pp.613-623
DOI: 10.1042/CS20150693
PMID: 26795436
PMCID: PMC5036530
NLM abbreviation: Clin Sci (Lond)
ISSN: 0143-5221
eISSN: 1470-8736
Grant note: HL007485 / NHLBI NIH HHS K08 HD050359 / NICHD NIH HHS HD050359 / NICHD NIH HHS T35 HL007485 / NHLBI NIH HHS R01 HL102659 / NHLBI NIH HHS
Language: English
Date published: 04/2016
Academic Unit: Critical Care; Cardiology; Stead Family Department of Pediatrics; Neonatology; Internal Medicine
Record Identifier: 9984093341802771

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