ICHIHARA Atsuhiro
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.
Journal Formal name:American journal of physiology. Renal physiology
Abbreviation:Am J Physiol Renal Physiol
ISSN code:15221466(Electronic)15221466(Linking)
Volume, Issue, Page pp.ajprenal.00088.2016
Author and coauthor Ramkumar Nirupama†, Stuart Deborah, Mironova Elena, Bugay Vladislav, Wang Shuping, Abraham Nikita, ICHIHARA Atsuhiro, Stockand James D, Kohan Donald E
Publication date 2016/04
Summary UNASSIGNED: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 investigaUNASSIGNED:ted 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 prorenin effect was prevented by protein kinase A and Akt inhibition, but unaffected by blockade of AT-1, ERK1/2 or p38 MAPK pathways. Taken together, these data indicate that renal tubular PRR, likely via direct prorenin/renin stimulation of PKA/Akt-dependent pathways, stimulates CD ENaC activity. Absence of renal tubular PRR promotes Na(+)wasting and reduces the hypertensive response to Ang-II.
DOI 10.1152/ajprenal.00088.2016
PMID 27053687