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Activation of collecting duct NOS1β during high salt feeding is critical for down‐regulation of Na + and K + transporters, in part, via down‐regulation of aldosterone
Author(s) -
Hyndman Kelly A,
Collins Jessika D,
Pollock Jennifer S
Publication year - 2017
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.31.1_supplement.1026.6
Subject(s) - aldosterone , endocrinology , medicine , chemistry , potassium , mineralocorticoid , sodium , plasma renin activity , renin–angiotensin system , propylthiouracil , biology , hormone , blood pressure , organic chemistry
We determined that deletion of nitric oxide synthase‐1β (NOS1β) from the collecting duct (CD) results in inappropriate ENaC activation during high salt diet. Given that sodium influx via ENaC is a driving force for potassium (K) secretion, we hypothesized that CD NOS1β regulates potassium handling. Male control and CDNOS1KO mice were placed on either 1) 0.4% NaCl + 1% K diet, NSNK, 2) 4% NaCl + 1% K diet, HSNK, 3) 0.4% NaCl + 0% K diet, NSLK, or 4) 4% NaCl + 0% K diet, HSLK, for 3 – 4 days. Food and water intake was similar between genotypes. As expected, plasma potassium was similar between NSNK (control 4.8 ± 0.3; KO 4.6 ± 0.2 mM) and HSNK (control 4.6 ± 0.4; KO 4.6 ± 0.1 mM), regardless of the genotype; however it was significantly reduced in the NSLK (control 3.9 ± 0.2; KO 3.5 ± 0.1 mM) and HSLK treatments (control 3.5 ± 0.1; KO 4.1 ± 0.2 mM). Plasma aldosterone failed to be suppressed in the CDNOS1KO mice on HSNK diet (control 74 ± 5; KO 422 ± 64 pg/ml, P < 0.05). Interestingly, plasma renin concentration was appropriately suppressed in both genotypes on HSNK diet. However, plasma aldosterone was appropriately suppressed in both genotypes on the potassium deficient diets (NSLK: control 81 ± 41, KO 177 ± 48 pg/ml; HSLK: control 95 ± 25, KO 100 ± 32 pg/ml). CDNOS1KO mice given spironolactone pellets (50 mg/kg b.w.) for 7 days while on a HSNK diet presented with significantly higher plasma potassium compared to controls with similar treatment (4.2 ± 0.07 mM vs. 3.9 ± 0.1 mM, P = 0.04). Western blot analysis of renal cortical lysates determined that during HSNK feeding CDNOS1KO mice display increased Kir4.1 potassium channel expression, increased NCC activation, increased NKCC2 expression, and ENaC activation compared to control cortical lysates. These data suggest that activation of NOS1β in the CD during high salt feeding modulates not only sodium handling but also potassium handling, in part, via down‐regulation of aldosterone. Support or Funding Information Research reported in this publication was supported by NIH NIDDK under award number K01DK105038 to K.A.H. and NIH NHLBI under award number P01HL95499 to J.S.P.