The Putative (Pro)renin Receptor Blocker HRP Fails to Prevent (Pro)renin Signaling
| Autor: | Ralf Dechend, Ulrike Maschke, Sandra Feldt, Friedrich C. Luft, Dominik N. Müller |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Vascular smooth muscle Blood Pressure Biology Muscle Smooth Vascular chemistry.chemical_compound Fumarates Internal medicine Renin–angiotensin system Renin medicine Animals Humans Receptor Kinase Angiotensin II General Medicine Aliskiren Amides Rats Endocrinology Basic Research chemistry Nephrology Mitogen-activated protein kinase Hypertension biology.protein Signal transduction Oligopeptides |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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