Grants and Contracts Details


Obesity is considered to be a primary contributor to the rising prevalence of hypertension. In general, the prevalence of hypertension is considered to be greater in men than in women until menopause, which is associated with both increased body weight gain and increased blood pressure. Studies in our laboratory indicate an activated adipocyte renin-angiotensin system (RAS) as a link between obesity and hypertension. Moreover, we have identified angiotensin-converting enzyme 2 (ACE2), which cleaves angiotensin II (AngII) to form the vasodilator angiotensin-1-7 (Ang-(1-7)), as a critical component of the RAS contributing to sex differences in the development of obesity-associated hypertension. We demonstrated that expanded adipose tissue during obesity can serve as a source of systemic AngII and is associated with the development of obesity-hypertension in male mice. High fat (HF)-fed male mice, with obesity-hypertension and increased plasma concentrations of AngII, exhibited decreased abundance of ACE2 in adipose tissue and decreased plasma concentrations of Ang-(1-7) at the low level of an ACE2 knockout. In contrast, HF-fed female mice, which were normotensive despite the development of obesity, displayed increased adipose activity of ACE2 which was associated with increased plasma concentrations of Ang-(1-7). Whole-body deficiency of ACE2 converted obese females to a hypertensive phenotype. In addition, we have demonstrated that ovariectomy (Ovx) reduced adipose ACE2 activity and plasma Ang-(1-7) concentrations in HF-fed female mice resulting in the development of obesity-hypertension. Administration of estrogen to Ovx females stimulated ACE2 activity in adipose tissue and restored protection against obesity-hypertension in wild-type but not ACE2-deficient mice. Taken together, these data suggest that activity of ACE2 in adipocytes plays a key role in blood pressure regulation during obesity through regulation of systemic levels of AngII versus Ang-(1-7). The central hypothesis of this study is that the balance of AngII versus Ang(-1-7), dictated by adipocyte ACE2, is different in males versus females, contributing to sex differences in the development of obesity-hypertension. We hypothesize that females are protected against the development of obesity-hypertension due to increased activity of ACE2 in adipocytes, and that stimulation of ACE2 activity in males will prevent the development of obesity-hypertension.
Effective start/end date1/1/1712/31/17


  • American Heart Association Great Rivers Affiliate: $48,600.00


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