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.