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Acute Angiotensin II Effects On NCC are Dependent on WNK4
Author(s) -
Ko Benjamin,
Hansen Lauren,
Mistry Abinash,
Mallick Rickta,
Hoover Robert
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1152.1
Subject(s) - angiotensin ii , cotransporter , endocrinology , medicine , chemistry , receptor , renin–angiotensin system , sodium , biology , organic chemistry , blood pressure
Acutely, angiotensin II (AII) is known to affect sodium chloride cotransporter (NCC) abundance and surface expression (SE). A possible role for WNK4 in mediating effects of AII on NCC has been described. To study this in a mammalian cell model, RNAi was used on mDCT15 cells to generate a WNK4 knock‐down cell line (WNK4KD). Thiazide‐sensitive 22 Na + uptake assays in mDCT15 cells showed a dose response to AII, peaking at 10 −11 M. mDCT15 cells showed a time dependent increase in activity, with peak response at 60 min (40±4%, p<0.01). An angiotensin receptor blocker eliminated this effect. WNK4 knock down in WNK4KD cells was measured via real time PCR to be 50±3%. WNK4KD cells did not show a statistically significant increase in activity with AII. NCC SE as measured by biotinylation and densitometry increased in mDCT15 cells with AII, peaking at 30 min (100±14%, p<0.01). There was a modest but statistically significant increase in SE at 30 min in WNK4KD cells (43±15%, p<0.05). These findings indicate a critical role for WNK4 in mediating acute effects of AII on NCC and provide a foundation to examine the mechanisms by which this occurs. Support K08 DK081728 (BK), R01 DK‐085097, VA Research Service (RH)