title: Oral oestrogen reverses ovariectomy-induced morning surge hypertension in growth-restricted mice.
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.
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Haskell
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
authors.forename: Veronica
authors.initials: V
authors.lastname: Peotta
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Reinking
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
authors.forename: Catherine
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
authors.forename: Vivian
authors.initials: V
authors.lastname: Zhu
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kenkel
authors.affiliation: Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, U.S.A. robert-roghair@uiowa.edu.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Roghair
mesh_terms: D000222:Adaptation, Physiological; D000284:Administration, Oral; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight; D002319:Cardiovascular System / Q000187:drug effects* / Q000294:innervation; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010052:Ovariectomy; D013997:Time Factors
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D005730:Ganglionic Blockers; D018733:Nicotinic Antagonists; D004958:Estradiol
keywords: autonomic; developmental origins; echocardiography; heart rate variability