Effect of HRP Upon the Expression and Intracellular Signaling of PRR in Cardiovascular and Renal Systems in Preeclamptic Rats Offspring

Abstract

Introduction Preeclampsia (PE) is a condition that affects both, the mother and the child, conditioning in both a greater susceptibility to develop cardiovascular diseases in future stages. It has been studied that prorenin renin receptor (PRR) has a broad participation in the cardiovascular system of PE products, it seems to play an important role in the development of future conditions, such as arterial hypertension, involving the renin angiotensin aldosterone system (RAS). RAS hyperactivity has been implicated as a cardiovascular risk factor in patients who come from a pregnancy complicated by preeclampsia. Mechanisms mediating fetal programming of adult arterial hypertension are numerous, including vascular dysfunction and reduction of the density of the arterioles and capillaries. Handle Region Peptide (HRP) is a decoy peptide that can inhibit the binding of prorrenin to the PRR receptor. HRP mimics the loop region and therefore competitively binds to the receptor, thus preventing receptor-mediated activation of prorenin and reducing its activity in tissue. Objective To evaluate the HRP blockade upon the PRR receptor and its transduction pathways: WNT and MAPK in cardiovascular and renal tissue in offspring from a pre-eclampsia model. Material and methods Male and female offspring from PE and healthy pregnant wistar rats, with 30 and 120 days of age, where set up in groups with or without HRP treatment (0.2 mg/Kg, subcutaneously for 7 days before sacrifice). We measured blood pressure by tail-cuff method. At the end of the treatment the expression of PRR, DVL1, beta-catenin, PKC-alpha were measured by immunoblot and RT-PCR in cardiovascular and renal tissue. Results Offspring from PE rats showed sustained high blood pressure, both male and female at 30 and 120 days. HRP treatment reverted partially this increase. All PE-derived groups showed an increase in PRR expression in aorta, heart and kidney. WNT and MAPK pathways also seemed to be activated in PE-derived animals, as shown by β-catenin, DVL-1 and PKCa increased expression. These findings are important because WNT signaling pathway is associated with kidney diseases and cardiac hypertrophy. Besides, this work shows that PRR participates in high blood pressure development in offspring derived from PE pregnancies.