Cardiomyocytes Bind and Activate Renal But not Non-Renal Human Prorenin.

Abstract

P10 Cardiomyocytes bind and internalize recombinant human prorenin (rhPR) and renin via mannose 6-phosphate (M6P) receptors (van Kesteren et al., Hypertension 1997). PR binding is followed by intracellular activation. Here we investigated 1) whether cardiomyocytes bind native human (pro)renin ((P)R) from various sources and 2) whether PR binding is followed by activation. Myocytes were isolated from Wistar rat pups by enzymatic dissociation and grown to confluence (6 x 10 5 cells in 3.8 cm 2 wells). Cells were incubated with rhPR, human plasma (obtained from captopril-treated patients (CAP), patients with renal artery stenosis (RAS) and anephric subjects (Nx)), or human amniotic fluid (HAF), diluted in DMEM (final volume 0.4 mL), for 4 hrs at 37°C, either with or without 10 mM M6P. Cell-associated R and PR, the latter following prior activation by plasmin, were determined by enzyme-kinetic assay. Results: See Table. Intracellular PR activation is reflected by the higher R/PR ratio in the cell lysates as compared to the medium. Conclusions: Cardiomyocytes bind and activate native human PR from renal (CAP & RAS), but not from non-renal (Nx & HAF) sources in a M6P- dependent manner. These data suggest that renal PR is meant to be sequestered by nonrenin-producing tissues in order to contribute to local angiotensin production, whereas non-renal PR functions at its production site only.