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Review
. 2015 Jan;42(1):14-21.
doi: 10.1111/1440-1681.12319.

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

Alexis A Gonzalez  1 , Minolfa C Prieto
Affiliations
Review

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

Alexis A Gonzalez et al. Clin Exp Pharmacol Physiol. 2015 Jan.

Abstract

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 (AT1 R), 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.

Keywords: angiotensin II-dependent hypertension; collecting duct; prorenin receptor; renin; renin-angiotensin system.

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Figures

Figure 1
Figure 1
A. Renin expression in juxtaglomerular cells (insert in red and arrow) and in collecting ducts (red). Brown color indicates aquaporin-2 (AQP-2) immunostaining, which is a specific marker for principal cells of the collecting duct. B. Renin immunolabeling in collecting ducts of a control rat; C. Renin is augmented in collecting ducts of Ang II infused rats. D. In Angiotensin II infused rats AT1 receptor antagonist blunted this effect. (modified from Prieto-Carrasquero et al., 2004; 2005).
Figure 2
Figure 2
Prorenin receptor, Anion Exchanger-1 and renin in normal rat kidney tissues. A. (Pro)renin receptor (arrows, green; apical cell side) is co-expressed with anion exchanger type 1 (arrow head, red; basolateral cell side), a marker for intercalated cells. B. (Pro)renin receptor is present in intercalated cells (green) while renin is expressed in principal cells (red, as noticed by the positive control of positive renin juxtaglomerular cells, arrow). Augmented renin/prorenin and (pro)renin receptor in Ang II-dependent hypertensive rats suggest that an interaction between both components may contribute to intratubular Ang I and Ang II formation and activation of PRR signaling pathways. Blue: DAPI; 4′,6-diamidino-2-phenylindole, nuclei marker.
Figure 3
Figure 3
Immunocytochemical evidence of the expression of renin in principal cells (red) and (pro)renin receptor (green) in intercalated cells in M-1 collecting duct cell line. Blue (DAPI; 4′,6-diamidino-2-phenylindole) is a nuclei marker. The image demonstrates close interaction between principal cells; the source of renin and prorenin and intercalated cells that expressing the (pro)renin receptor.
Figure 4
Figure 4
Expression of the (P)RR in medullary collecting ducts in normal rats (A) and Ang II infused rats for 14 days. Ang II infusion causes a decrease in the number of positive cells. Despite decrease in cells with immunoreactivity for (pro)renin receptor bound to the membrane, the soluble cleaved form of the (pro)renin receptor was augmented in medullary tissues and importantly detected in the urine of the Ang II infused rats (C). Ang II infusion for 14 days also causes the augmentation of renin and prorenin in the collecting ducts suggesting that (pro)renin receptor and renin can interact to contribute to Ang I formation and further Ang II generation (modified from Gonzalez et al., 2011).
Figure 5
Figure 5
Hypothetic role the (pro)renin receptor in collecting ducts and intercalated cells in response to Ang II. Ang II stimulates prorenin and renin synthesis in principal cells of the collecting ducts as well as (P)RR levels. The (P)RR activates ERK 1/2 pathways stimulating COX-2 expression.
Figure 6
Figure 6
Specific cell type localization of the (P)RR in the collecting ducts of rat kidneys. (P)RR positive cells showed specific immunostaining at the apical side (A) in green color, the absence of merging colors (C) indicates that (P)RR receptor is not co-localized with aquaporin-2 (B; red). The co-localization of apical (pro)renin receptor (D, G, J; green,) with apical Rhcg (E, H; red) or with basolateral Rhbg (K; red) is demonstrated in panels F, I and L, respectively. D, E, F: cortex; G, H, I, J, K, L: medulla.
See this image and copyright information in PMC

References

    1. Borensztein P, Germain S, Fuchs S, Philippe J, Corvol P, Pinet F. cis-Regulatory elements and trans-acting factors directing basal and cAMP-stimulated human renin gene expression in chorionic cells. Circ Res. 1994;74:764–73. - PubMed
    1. Castrop H, Hocherl K, Kurtz A, Schweda F, Todorov V, Wagner C. Physiology of kidney renin. Physiol Rev. 2010 Apr;90(2):607–73. - PubMed
    1. Muller MW, Todorov V, Kramer BK, Kurtz A. Angiotensin II inhibits renin gene transcription via the protein kinase C pathway. Pflugers Arch. 2002 Jul;444(4):499–505. - PubMed
    1. Seikaly MG, Arant BS, Jr., Seney FD., Jr. Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest. 1990;86:1352–7. - PMC - PubMed
    1. Prieto-Carrasquero MC, Harrison-Bernard LM, Kobori H, Ozawa Y, Hering-Smith KS, Hamm LL, et al. Enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Hypertension. 2004 Aug;44(2):223–9. - PMC - PubMed

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