Collecting duct principal, but not intercalated, cell (pro)renin receptor modulates sodium and water transport

Abstract

The collecting duct (CD) is the predominant site for prorenin receptor (PRR) expression within the nephron. We have previously demonstrated that the CD PRR regulates epithelial Na+ channel (ENaC) activity and water transport; however, which CD cell type is involved is unclear. Hence, we examined the effects of principal cell (PC) or intercalated cell (IC) PRR deletion on renal Na+ and water handling. PC or IC PRR KO mice were obtained by crossing floxed PRR mice with mice harboring Cre recombinase under the control of the AQP2 or B‐1 subunit of the H+ ATPase promoters, respectively. In‐situ hybridization using RNAscope demonstrated abundant PRR RNA in IC with modest staining in PC in control mice with reduced cell‐specific PRR RNA in PC and IC KO mice. Compared to controls, PC KO, but not IC KO mice, had increased urinary volume (Control: 1.2 ± 0.4 vs PC KO: 2.0 ± 0.3, P < 0.05; IC KO: 1.4 ± 0.2 ml/day), reduced urine osmolality (Control: 3160 ± 279 vs PC KO: 2343 ± 247, P < 0.05; IC KO: 2748 ± 356 mosm/Kg H2O) and reduced expression of renal medullary AQP2 (50% of control). Further, PC KO mice had reduced renal medullary ENaC‐α expression with normal and low Na+ diet and lower Na+ balance (24‐hour intake – excretion) following low Na+ intake (controls: 60.5 ± 7.5 vs PC KO: 25.7 ± 10.6 μmol/day, P <0.05). In contrast, no differences in Na+ balance or ENaC expression was observed between control or IC KO mice. In acutely isolated cortical CD, under basal conditions, no significant differences in ENaC activity were observed between control, PC or IC specific PRR KO mice. Treatment with mouse prorenin (10 nM for 30 min) increased ENaC channel number and open probability by 2‐fold in control mice (basal: 0.15 ± 0.04; prorenin treatment: 0.74 ± 0.25). Addition of prorenin did not alter ENaC activity in PC specific PRR KO mice (basal: 0.28 ± 0.06; prorenin treatment: 0.33 ± 0.13) but increased ENaC activity in IC specific PRR KO mice (basal: 0.17 ± 0.08; prorenin treatment 1.29 ± 0.13). However, mean arterial pressure as measured by telemetry (Controls: 104 ± 1, PC KO: 106 ± 2, IC KO: 101 ± 4 mm Hg) was similar between controls and PC or IC KO mice on normal and low Na+ diets. Taken together, these findings indicate that under physiologic conditions, the PC, but not IC, PRR modulates ENaC expression and activity, urinary Na+ excretion and water transport. Further studies are needed to examine the role of PC and IC PRR in pathological states such as Ang‐II induced hypertension.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.