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High aminopeptidase A activity contributes to blood pressure control in ob/ob mice by AT2 receptor-dependent mechanism

Item Type:Article
Title:High aminopeptidase A activity contributes to blood pressure control in ob/ob mice by AT2 receptor-dependent mechanism
Creators Name:Morais, R.L. and Hilzendeger, A.M. and Visniauskas, B. and Todiras, M. and Alenina, N. and Mori, M.A. and Araújo, R.C. and Nakaie, C.R. and Chagas, J.R. and Carmona, A.. and Bader, M. and Pesquero, J.B.
Abstract:Obesity is assumed to be a major cause of human essential hypertension, however the mechanisms responsible for weight-related increase in blood pressure (BP) are not fully understood. The prevalence of hypertension induced by obesity has grown over the years and the role of the renin-angiotensin-aldosterone system (RAAS) in this process continues to be elucidated. In this scenario, the ob/ob mice are a genetic obesity model generally used for metabolic disorders studies. These mice are normotensive even though they present several metabolic conditions that predispose them to hypertension. Although the normotensive trait in these mice is associated with the poor activation of sympathetic nervous system by the lack of leptin, we demonstrated that ob/ob mice present massively increased aminopeptidase A (APA) activity in the circulation. APA enzyme metabolizes angiotensin (Ang) II into Ang III, a peptide associated with intrarenal angiotensin type (AT) 2 receptor activation and induction of natriuresis. In these mice, we found increased Ang III levels in the circulation, high AT2 receptor expression in the kidney and enhanced natriuresis. AT2 receptor blocking and APA inhibition increased BP, suggesting the Ang III-AT2 receptor axis as a complementary BP control mechanism. Circulating APA activity was significantly reduced by weight loss independently of leptin, indicating the role of fat tissue in APA production. Therefore, in this study we provide new data supporting the role of APA in BP control in ob/ob mouse strain. These findings improve our comprehension about obesity-related hypertension and suggest new tools for its treatment.
Keywords:Aminopeptidase A, Hypertension, Obesity, Renin-Angiotensin-Aldosterone System, Animals, Mice
Source:American Journal of Physiology Heart and Circulatory Physiology
Publisher:American Physiological Society
Page Range:H437-H445
Date:1 March 2017
Official Publication:https://doi.org/10.1152/ajpheart.00485.2016
PubMed:View item in PubMed

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