High aminopeptidase A activity contributes to blood pressure control in ob/ob mice by AT(2) receptor-dependent mechanism

High aminopeptidase A activity contributes to blood pressure control in ob/ob mice by AT(2) receptor-dependent mechanism

Author Morais, Rafael L. Autor UNIFESP Google Scholar
Hilzendeger, Aline M. Autor UNIFESP Google Scholar
Visniauskas, Bruna Autor UNIFESP Google Scholar
Todiras, Mihail Google Scholar
Alenina, Natalia Google Scholar
Mori, Marcelo A. Autor UNIFESP Google Scholar
Araujo, Ronaldo C. Autor UNIFESP Google Scholar
Nakaie, Clovis R. Autor UNIFESP Google Scholar
Chagas, Jair R. Autor UNIFESP Google Scholar
Carmona, Adriana K. Autor UNIFESP Google Scholar
Bader, Michael Google Scholar
Pesquero, Joao B. Autor UNIFESP Google Scholar
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 disorder 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 2 (AT(2)) receptor activation and induction of natriuresis. In these mice, we found increased ANG-III levels in the circulation, high AT(2) receptor expression in the kidney, and enhanced natriuresis. AT(2) receptor blocking and APA inhibition increased BP, suggesting the ANG III-AT(2) 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. NEW & NOTEWORTHY In this study, we reported an increased angiotensin III generation in the circulation of ob/ob mice caused by a high aminopeptidase A activity. These findings are associated with an increased natriuresis found in these mice and support the role of renin-angiotensin-aldosterone system as additional mechanism regulating blood pressure in this genetic obese strain.
Keywords aminopeptidase A
hypertension
obesity
renin-angiotensin-aldosterone system
ob/ob mice
xmlui.dri2xhtml.METS-1.0.item-coverage Bethesda
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
Date 2017
Published in American Journal Of Physiology-Heart And Circulatory Physiology. Bethesda, v. 312, n. 3, p. H437-H445, 2017.
ISSN 0363-6135 (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent H437-H445
Origin http://dx.doi.org/10.1152/ajpheart.00485.2016
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000397808500010
URI https://repositorio.unifesp.br/handle/11600/55035

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