Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Arteriosclerosis, thrombosis, and vascular biology, 2012-06, Vol.32 (6), p.1392-1399

Ort / Verlag

United States

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. These results demonstrate that tissue-specific regulation of ACE2 by diet and sex hormones contributes to sex differences in obesity-hypertension.