Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.

Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.
Am J Physiol Renal Physiol. 2016 Apr 6;:ajprenal.00088.2016
Authors: Ramkumar N, Stuart D, Mironova E, Bugay V, Wang S, Abraham N, Ichihara A, Stockand JD, Kohan DE
Abstract
The physiological significance of the renal tubular prorenin receptor (PRR) has been difficult to elucidate due to developmental abnormalities associated with global or renal-specific PRR knockout (KO). We recently developed an inducible renal tubule-wide PRR KO using the Pax8/LC1 transgenes and demonstrated that disruption of renal tubular PRR at 1 month of age caused no renal histological abnormalities. Here, we examined the role of renal tubular PRR in blood pressure (BP) regulation and Na(+)excretion and investigated the signaling mechanisms by which PRR regulates Na(+)balance. No detectable differences in BP were observed between control and PRR KO mice fed normal or low Na(+)diets. However, compared to controls, PRR KO mice had elevated plasma renin concentration and lower cumulative Na(+)balance with normal and low Na(+)intake. PRR KO mice had an attenuated hypertensive response and reduced Na(+)retention following angiotensin-II infusion. Further, PRR KO mice had significantly lower epithelial Na(+)channel (ENaC-α) expression. Treatment with mouse prorenin increased, while PRR antagonism decreased, ENaC activity in isolated split-open collecting ducts (CD). The...

Source: Am J Physiol Renal P... - April 5, 2016 Category: Urology & Nephrology Authors: Ramkumar N, Stuart D, Mironova E, Bugay V, Wang S, Abraham N, Ichihara A, Stockand JD, Kohan DE Tags: Am J Physiol Renal Physiol Source Type: research