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

Tools

Item Type:	Article
Title:	The putative (pro)renin receptor blocker HRP fails to prevent (pro)renin signaling
Creators Name:	Feldt, S., Maschke, U., Dechend, R., 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
ISSN:	1046-6673
Publisher:	American Society of Nephrology
Volume:	19
Number:	4
Page Range:	743-748
Date:	April 2008
Official Publication:	https://doi.org/10.1681/ASN.2007091030
PubMed:	View item in PubMed

Repository Staff Only: item control page