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The putative (pro)renin receptor blocker HRP fails to prevent (pro)renin signaling

Item Type:Article
Title:The putative (pro)renin receptor blocker HRP fails to prevent (pro)renin signaling
Creators Name:Feldt, S. and Maschke, U. and Dechend, R. and Luft, F.C. and Mueller, D.N.
Abstract:The prorenin/renin receptor is a recently discovered component of the renin-angiotensin system. The effects of aliskiren, a direct inhibitor of human renin, were compared with the handle region decoy peptide (HRP), which blocks the prorenin/renin receptor, in double-transgenic rats overexpressing the human renin and angiotensinogen genes. After 7 wk, all aliskiren-treated rats were alive, whereas mortality was 40% in vehicle-treated and 58% in HRP-treated rats. Aliskiren but not the HRP reduced BP and normalized albuminuria, cystatin C, and neutrophil gelatinase-associated lipocalin, a marker of renal tubular damage, to the levels of nontransgenic controls. In vitro, human renin and prorenin induced extracellular signal-regulated kinase 1/2 phosphorylation, independent of angiotensin II (AngII), in vascular smooth muscle cells. Preincubation with the HRP or aliskiren did not prevent renin- and prorenin-induced extracellular signal-regulated kinase 1/2 phosphorylation, whereas the MAP kinase kinase (MEK1/2) inhibitor PD98059 prevented both. In conclusion, renin inhibition but not treatment with the HRP protects against AngII-induced renal damage in double-transgenic rats. In addition, the in vitro data do not support the use of the HRP to block AngII-independent prorenin- or renin-mediated effects.
Keywords:Animals, Rats
Source:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
Page Range:743-748
Date:April 2008
Official Publication:https://doi.org/10.1681/ASN.2007091030
PubMed:View item in PubMed

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