Aliskiren Modifies Canonical Wnt/β‐Catenin Signaling Pathway Associated to (Pro)renin Receptor on Heart and Kidney in 5/6 Nephrectomy‐Induced Hypertension in Rats

Abstract

The Wnt/frizzled receptor signaling pathways are important in morphogenesis and development of essential organs. (Pro)renin receptor (PRR) has been characterized as a multifunctional protein associated with vacuolar H+‐ATPase (v‐H+‐ATPase) (independently of renin) and is required for canonical Wnt/β‐catenin signaling activation. Aliskiren, a direct renin inhibitor, has been used to treat cardiovascular disorders. The aim of this work was to study Aliskiren effects upon PRR and canonical Wnt/β‐catenin pathway in cardiac and renal tissue during 5/6 nephrectomy (5/6 Nx)‐induced hypertension. Male Wistar rats underwent 5/6 Nx or sham operation (S), and were treated with Aliskiren, 10 mg/kg/day/7 days. Control groups received vehicle. 24‐hour urine was collected and blood pressure was measured at the end of experiment. PRR, β‐catenin and dishevelled (Dvl‐1) expression was determined by immunoblot. Our results showed that, compared to sham animals, 5/6 Nx rats treated with Aliskiren had lowered blood pressure and improved seric creatinine, proteinuria and creatinine clearance. We found in nephrectomized rats that PRR expression increased in heart and kidney seven days after surgery, and aliskiren reduced PRR, β‐catenin and Dvl‐1 expression in both tissues. These results confirm the antihypertensive and renoprotective effects of aliskiren and interestingly, showed that aliskiren modifies PRR expression as well as canonical Wnt/β‐catenin signaling expression. Supported by SIP20140636 grant