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Vasopressin Type 2 Receptor (V2R) Activation Increases Renin Expression in Mouse Renal Collecting Duct Cells through cAMP/PKA/CREB Pathway

Renin synthesis in juxtaglomerular (JG) cells is mediated by intracellular cAMP accumulation and activation of PKA/CREB pathway. We have demonstrated that renin is also expressed in the principal cells of the collecting duct (CD) and that its synthesis is increased in rodent models of angiotensin (Ang) II‐dependent hypertension, despite the suppression of renin in JG cells. Vasopressin is one of the final effectors of the renin angiotensin system (RAS). Vasopressin type 2‐receptor (V2R) activation leads to the activation of cAMP/PKA/CREB pathway and aquaporin‐2 expression in the apical plasma membrane of principal cells of the CD. We hypothesize that the activation of V2R increases renin synthesis in mouse CD cells through PKA/CREB pathway. Desmopressin (DDAVP 10‐6 mol/L, 4 h), a selective V2R agonist, increased renin mRNA and prorenin/renin protein levels in cell lysate and culture media in M‐1 CD cell line, while co‐treatment with DDAVP + H89 (PKA inhibitor) prevented this effect. DDAVP also increased CREB phosphorylation and CREB nuclear localization, while H89 blunted this effect. In mice subjected to 48 h of water deprivation, renin was increased in renal medullary CDs. Because water deprivation may indirectly activate RAS, we evaluated the effect of AngII plus DDAVP in M‐1 CD cells. Combined treatment further increased prorenin protein expression suggesting that AngII may enhance stimulation of cAMP accumulation and PKA/CREB pathway. These results indicate that the activation of V2R stimulates renin synthesis in CD cells via PKA/CREB pathway.