Renin and the (pro)renin receptor in the renal collecting duct: Role in the pathogenesis of hypertension

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Abstract

Summary: The intrarenal renin-angiotensin system (RAS) plays a critical role in the pathogenesis and progression of hypertension and kidney disease. In angiotensin (Ang) II-dependent hypertension, collecting duct renin synthesis and secretion are stimulated despite suppression of juxtaglomerular (JG) renin. This effect is mediated by the AngII type I receptor (AT1R), independent of blood pressure. Although the regulation of JG renin has been extensively studied, the mechanisms by which renin is regulated in the collecting duct remain unclear. The augmentation of renin synthesis and activity in the collecting duct may provide a pathway for additional generation of intrarenal and intratubular AngII formation due to the presence of angiotensinogen substrate and angiotensin-converting enzyme in the nephron. The recently described (pro)renin receptor ((P)RR) binds renin or prorenin, enhancing renin activity and fully activating the biologically inactive prorenin peptide. Stimulation of (P)RR also activates intracellular pathways related to fibrosis. Renin and the (P)RR are augmented in renal tissues of AngII-dependent hypertensive rats. However, the functional contribution of the (P)RR to enhanced renin activity in the collecting duct and its contribution to the development of hypertension and kidney disease have not been well elucidated. This review focuses on recent evidence demonstrating the mechanism of renin regulation in the collecting ducts and its interaction with the (P)RR. The data suggest that renin-(P)RR interactions may induce stimulation of intracellular pathways associated with the development of hypertension and kidney disease.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume42
Issue number1
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Angiotensin II-dependent hypertension
  • Collecting duct
  • Prorenin receptor
  • Renin
  • Renin-angiotensin system

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