Administration of 17β-estradiol to ovariectomized obese female mice reverses obesity-hypertension through an ACE2-dependent mechanism

Yu Wang, Robin Shoemaker, Sean E. Thatcher, Frederique Batifoulier-Yiannikouris, Victoria L. English, Lisa A. Cassis

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

We recently demonstrated that female mice are resistant to the development of obesity-induced hypertension through a sex hormone-dependent mechanism that involved adipose angiotensin-converting enzyme 2 (ACE2). In this study, we hypothesized that provision of 17β-estra-diol (E2) to ovariectomized (OVX) high-fat (HF)-fed female hypertensive mice would reverse obesity-hypertension through an ACE2-dependent mechanism. Pilot studies defined dose-dependent effects of E2 in OVX female mice on serum E2 concentrations and uterine weights. An E2 dose of 36 (μg/ml restored normal serum E2 concentrations and uterine weights. Therefore, HF-fed OVX female Ace2+I +and Ace2-/- mice were administered vehicle or E2 (36 μg/ml) for 16 wk. E2 administration significantly decreased body weights of HF-fed OVX female Ace2+I+ and Ace2-/-mice of either genotype. At 15 wk, E2 administration decreased systolic blood pressure (SBP) of OVX HF-fed Ace2+I+ but not Ace2-/- females during the light but not the dark cycle. E2-mediated reductions in SBP in Ace2+I+ females were associated with significant elevations in adipose ACE2 mRNA abundance and activity and reduced plasma ANGII concentrations. In contrast to females, E2 administration had no effect on any parameter quantified in HF-fed male hypertensive mice. In 3T3-L1 adipocytes, E2 promoted ACE2 mRNA abundance through effects at estrogen receptor-α (ERα) and resulted in ERa-mediated binding at the ACE2 promoter. These results demonstrate that E2 administration to OVX females reduces obesity-induced elevations in SBP (light cycle) through an ACE2-dependent mechanism. Beneficial effects of E2 to decrease blood pressure in OVX obese females may result from stimulation of adipose ACE2.

Original languageEnglish
Pages (from-to)E1066-E1075
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume308
Issue number12
DOIs
StatePublished - Jun 15 2015

Bibliographical note

Publisher Copyright:
© 2015 American Physiological Society. All Rights Reseved.

Keywords

  • 17β-estradiol
  • Blood pressure
  • Ovariectomy
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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