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ICHIHARA Atsuhiro
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Professor and Division head |
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| 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 |