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, where...

Renin/prorenin binding to the (pro)renin receptor ([P]RR) results in direct (angiotensin-independent) secondmessenger activation in vitro, whereas in vivo studies in rodents overexpressing prorenin ( 400-fold) or the (P)RR do not support such activation. To solve this discrepancy, DNA synthesis, extracellular signal–regulated kinase 1/2 phosphorylation, and plasminogen-activator inhibitor 1 rel...

OBJECTIVE It has not yet been fully elucidated whether cardiac tissue levels of prorenin, renin and (P)RR are activated in hypertension with a high salt intake. We hypothesized that a high salt intake activates the cardiac tissue renin angiotensin system and prorenin-(pro)renin receptor system, and damages the heart at an early stage of hypertension. METHODS Wistar Kyoto rats (WKY) and sponta...

It is widely acknowledged that activation of the renin-angiotensin system impairs insulin sensitivity. Pharmacological inhibition of the (pro)renin receptor-dependent system has shown beneficial effects in diabetic nephropathy, retinopathy and hypertensive cardiac damage in animal models. Previously, we showed that fructose feeding stimulated nonproteolytic activation of prorenin and subsequent...

In addition to the juxtaglomerular apparatus, renin is also synthesized in renal tubular epithelium, including the collecting duct (CD). Angiotensin (Ang) II differentially regulates the synthesis of juxtaglomerular (inhibition) and CD (stimulation) renin. Because diabetes mellitus, a disease with high intrarenal renin-Ang system and Ang II activity, is characterized by high prorenin levels, we...

Cardiovascular Effects of Nonproteolytic Activation of Prorenin To the Editor: Several articles have appeared recently on the role of tissue prorenin in the pathogenesis of cardiovascular and renal damage in experimental models of hypertension and diabetes mellitus1–3 including the study by Ichihara et al,3 published in Hypertension and accompanied by an editorial comment.4 Thus, in rats with s...

AIMS The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. METHODS AND RESULTS PRR was expressed in human mammary arteries and in cultured human aortic SMCs. Prorenin induced SMC migration in a dose-dependent man...

In contrast to proteolytic activation of inactive prorenin by cleavage of the N-terminal 43 residue peptide, we found that prorenin is activated without proteolysis by binding of the prorenin receptor to the pentameric "handle region" I(11P)LLKK(15P). We hypothesized that such activation occurs in hypertensive rats and causes cardiac renin-angiotensin system (RAS) activation and end-organ damag...

The renin-angiotensin system (RAS) plays an important role in cardiovascular and renal physiology and disease, and the benefits of angiotensin-converting enzyme inhibitor, angiotensin type 1 receptor blocker, and renin inhibitor therapies are mediated in part by their modification of the levels and actions of angiotensin peptides. Despite its long history, the RAS remains an active area of rese...