Angiotensin Converting Enzyme 2 Contributes to Sex Differences in the Development of Obesity Hypertension in C57BL/6 Mice
- 1 June 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 32 (6), 1392-1399
- https://doi.org/10.1161/atvbaha.112.248559
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. Supplemental Digital Content is available in the text.This publication has 38 references indexed in Scilit:
- A polymorphism in ACE2 is associated with a lower risk for fatal cardiovascular events in females: the MORGAM projectJournal of the Renin-Angiotensin-Aldosterone System, 2011
- Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertensionAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2004
- Gender Differences in Angiotensin-Converting Enzyme (ACE) Activity and Inhibition by Enalaprilat in Healthy VolunteersJournal of Cardiovascular Pharmacology, 2004
- The Framingham Study: historical insight on the impact of cardiovascular risk factors in men versus women.2002
- Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort studyThe Lancet, 2001
- Gender differences in the attenuation of salt-induced hypertension by angiotensin (1-7)Peptides, 2001
- Molecular mechanisms of estrogen actions on the vasculatureJournal of Nuclear Cardiology, 2000
- Gender Differences in Development of Hypertension in Spontaneously Hypertensive RatsHypertension, 2000
- Trends in the Prevalence, Awareness, Treatment, and Control of Hypertension in the Adult US PopulationHypertension, 1995
- Metabolism of mammary, abdominal, and femoral adipocytes in women before and after menopauseMetabolism, 1986