Angiotensin converting enzyme 2 contributes to sex differences in the development of obesity hypertension in C57BL/6 mice

Manisha Gupte, Sean E. Thatcher, Carine M. Boustany-Kari, Robin Shoemaker, Frederique Yiannikouris, Xuan Zhang, Michael Karounos, Lisa A. Cassis

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

Objectives-Obesity promotes hypertension, but it is unclear if sex differences exist in obesity-related hypertension. Angiotensin converting enzyme 2 (ACE2) converts angiotensin II (AngII) to angiotensin-(1-7) (Ang-[1-7]), controlling peptide balance. We hypothesized that tissue-specific regulation of ACE2 by high-fat (HF) feeding and sex hormones contributes to sex differences in obesity-hypertension. Methods and Results-HF-fed females gained more body weight and fat mass than males. HF-fed males exhibiting reduced kidney ACE2 activity had increased plasma angiotensin II levels and decreased plasma Ang-(1-7) levels. In contrast, HF-fed females exhibiting elevated adipose ACE2 activity had increased plasma Ang-(1-7) levels. HF-fed males had elevated systolic and diastolic blood pressure that were abolished by losartan. In contrast, HF-fed females did not exhibit increased systolic blood pressure until females were administered the Ang-(1-7) receptor antagonist, D-Ala-Ang-(1-7). Deficiency of ACE2 increased systolic blood pressure in HF-fed males and females, which was abolished by losartan. Ovariectomy of HF-fed female mice reduced adipose ACE2 activity and plasma Ang-(1-7) levels, and promoted obesity-hypertension. Finally, estrogen, but not other sex hormones, increased adipocyte ACE2 mRNA abundance. Conclusions-These results demonstrate that tissue-specific regulation of ACE2 by diet and sex hormones contributes to sex differences in obesity-hypertension.

Original languageEnglish
Pages (from-to)1392-1399
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume32
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Angiotensin-(1-C7)
  • Blood pressure
  • Losartan
  • Ovariectomy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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