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

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dc.citation.issue3
dc.citation.volume312
dc.contributor.authorMorais, Rafael L. [UNIFESP]
dc.contributor.authorHilzendeger, Aline M. [UNIFESP]
dc.contributor.authorVisniauskas, Bruna [UNIFESP]
dc.contributor.authorTodiras, Mihail
dc.contributor.authorAlenina, Natalia
dc.contributor.authorMori, Marcelo A. [UNIFESP]
dc.contributor.authorAraujo, Ronaldo C. [UNIFESP]
dc.contributor.authorNakaie, Clovis R. [UNIFESP]
dc.contributor.authorChagas, Jair R. [UNIFESP]
dc.contributor.authorCarmona, Adriana K. [UNIFESP]
dc.contributor.authorBader, Michael
dc.contributor.authorPesquero, Joao B. [UNIFESP]
dc.coverageBethesda
dc.date.accessioned2020-07-17T14:02:48Z
dc.date.available2020-07-17T14:02:48Z
dc.date.issued2017
dc.description.abstractObesity is assumed to be a major cause of human essential hypertensionen
dc.description.abstracthowever, 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.en
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, Campus Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Psicobiol, Campus Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationMax Delbruck Ctr Mol Med, Berlin, Germany
dc.description.affiliationCharite Univ Med Berlin, Berlin, Germany
dc.description.affiliationGerman Ctr Cardiovasc Res, Berlin, Germany
dc.description.affiliationUniv Lubeck, Inst Biol, Lubeck, Germany
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biofis, Campus Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Psicobiol, Campus Sao Paulo, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior
dc.format.extentH437-H445
dc.identifierhttp://dx.doi.org/10.1152/ajpheart.00485.2016
dc.identifier.citationAmerican Journal Of Physiology-Heart And Circulatory Physiology. Bethesda, v. 312, n. 3, p. H437-H445, 2017.
dc.identifier.doi10.1152/ajpheart.00485.2016
dc.identifier.issn0363-6135
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55035
dc.identifier.wosWOS:000397808500010
dc.language.isoeng
dc.publisherAmer Physiological Soc
dc.relation.ispartofAmerican Journal Of Physiology-Heart And Circulatory Physiology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectaminopeptidase Aen
dc.subjecthypertensionen
dc.subjectobesityen
dc.subjectrenin-angiotensin-aldosterone systemen
dc.subjectob/ob miceen
dc.titleHigh aminopeptidase A activity contributes to blood pressure control in ob/ob mice by AT(2) receptor-dependent mechanismen
dc.typeinfo:eu-repo/semantics/article
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