High aminopeptidase A activity contributes to blood pressure control in ob/ob mice by AT2 receptor-dependent mechanism
| Autor: | João Bosco Pesquero, Clovis R. Nakaie, Rafael Leite Morais, Michael Bader, Jair R. Chagas, Natalia Alenina, Marcelo A. Mori, Adriana K. Carmona, Aline M Hilzendeger, Mihail Todiras, Bruna Visniauskas, Ronaldo C. Araujo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Receptor expression Leptin Angiotensin III 030204 cardiovascular system & hematology Biology Essential hypertension medicine.disease Natriuresis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Endocrinology Physiology (medical) Internal medicine Glutamyl aminopeptidase Renin–angiotensin system medicine Cardiology and Cardiovascular Medicine Receptor |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 312:H437-H445 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | 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 (AT2) 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. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|