Cyto-Protector Effect of a VDR Activator at the Mitochondrial Level in an Obstructive Nephropathy Model

LEON FERDER; WALTER MANUCHA

Orlando, Florida

Congreso; High Blood Pressure Research 2011; 2011

Inter-American Society of Hypertension (IASH), the American Heart Association's Council for High Blood Pressure Research and the Council on Kidney in Cardiovascular Disease

Background: Growing evidence proposes that vitamin D slows the progression of chronic kidney diseases. Further, activators of vitamin D receptors (VDR) have suppressant effect on the renin-angiotensin system (RAS), as well as anti-inflammatory and anti-fibrotic effects. Aim: This study was performed to evaluate in an obstructive nephropathy model (UUO), possible paricalcitol (Pari) cyto-protective effect at the mitochondrial level. Methods: Ten adult female rats were obstructed surgically and divided into two groups (control or treated). The treatment was done for 15-day duration (30ng/Kg). We evaluated: 1-parathyroid hormone, Ca+2 and P, 2-Fibrosis, apoptosis and mitochondrial morphology, 3-VDR, AT1 receptor, TGF-â and Renox (NOX4) expression and 4)-NADPH oxidase activity. Results: Biochemical, histological and molecular studies shows mitochondrial injury in UUO. Electronic microscopy revealed, electronically luminous nuclear material and the mitochondria were increased in size with dilated crests and spaces in their interior. Also, high AT1 expression and NADPH activity were reverts in paricalcitol-treated animals. Conclusions: These results suggest, in an obstructed nephropathy model, a cyto-protected effect of the activator of Vitamin D receptors, paricalcitol, revealing for the first time a possible protective effect AT1 receptor dependent at the mitochondrial level.