The macula densa prorenin receptor is essential in renin release and blood pressure control

The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS); however, recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site o...

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Veröffentlicht in:American journal of physiology. Renal physiology 2018-09, Vol.315 (3), p.F521-F534
Hauptverfasser: Riquier-Brison, Anne D M, Sipos, Arnold, Prókai, Ágnes, Vargas, Sarah L, Toma, Lldikó, Meer, Elliott J, Villanueva, Karie G, Chen, Jennifer C M, Gyarmati, Georgina, Yih, Christopher, Tang, Elaine, Nadim, Bahram, Pendekanti, Sujith, Garrelds, Ingrid M, Nguyen, Genevieve, Danser, A H Jan, Peti-Peterdi, János
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Sprache:eng
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Zusammenfassung:The prorenin receptor (PRR) was originally proposed to be a member of the renin-angiotensin system (RAS); however, recent work questioned their association. The present paper describes a functional link between the PRR and RAS in the renal juxtaglomerular apparatus (JGA), a classic anatomical site of the RAS. PRR expression was found in the sensory cells of the JGA, the macula densa (MD), and immunohistochemistry-localized PRR to the MD basolateral cell membrane in mouse, rat, and human kidneys. MD cell PRR activation led to MAP kinase ERK1/2 signaling and stimulation of PGE release, the classic pathway of MD-mediated renin release. Exogenous renin or prorenin added to the in vitro microperfused JGA-induced acute renin release, which was inhibited by removing the MD or by the administration of a PRR decoy peptide. To test the function of MD PRR in vivo, we established a new mouse model with inducible conditional knockout (cKO) of the PRR in MD cells based on neural nitric oxide synthase-driven Cre-lox recombination. Deletion of the MD PRR significantly reduced blood pressure and plasma renin. Challenging the RAS by low-salt diet + captopril treatment caused further significant reductions in blood pressure, renal renin, cyclooxygenase-2, and microsomal PGE synthase expression in cKO vs. wild-type mice. These results suggest that the MD PRR is essential in a novel JGA short-loop feedback mechanism, which is integrated within the classic MD mechanism to control renin synthesis and release and to maintain blood pressure.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00029.2018