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Collecting Duct NOS1 is Necessary to Maintain Sodium Balance in Male, But Not Female Mice
Author(s) -
Sedaka Randee S.,
Dunaway Luke S,
Allan J. Miller,
Holliday Alexis D.,
Almutlaq Rawan,
Hyndman Kelly A.,
Pollock Jennifer S.
Publication year - 2020
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.2020.34.s1.03772
Subject(s) - medicine , endocrinology , excretion , chemistry , sodium , urine , homeostasis , nitric oxide , metabolite , biology , organic chemistry
Nitric oxide synthase 1 (NOS1) is a well‐established regulator of fluid and electrolyte balance in the collecting duct (CD). We previously reported that a loss of CDNOS1 in male mice results in reduced sodium excretion, urine volume, and nitric oxide (NO) excretion as well as increased plasma sodium compared to flox control mice after being challenged with 1 day of high salt diet. However, it is not yet known if this genotype difference is conserved in female mice. Therefore, we investigated whether collecting duct NOS1 is critical in maintaining homeostasis in female mice. Female CDNOS1KO and flox control mice were acclimated to metabolic cages and placed on a sodium deficient (LS, 1 week) then challenged with a high sodium (HS, 1 day) diet and urine collected. Female CDNOS1KO mice and flox control mice had similar sodium excretion (Flox: 3.24±0.32, KO: 2.62±0.31mmol/day; n=8–12/group, p>0.05), urine volume (Flox: 7.69±0.75, KO: 6.42±0.82mL/day; n=8–12/group, p>0.05), and NOx excretion (Flox: 1099±205, KO: 1339±389 μmol/day; n=8–12/group, p>0.05) in addition to comparable plasma sodium levels (Flox: 146±1.0, KO: 147±0.5mmol/L; n=6/group, p>0.05) after one day of a high salt challenge. Furthermore, urinary prostaglandin E metabolite excretion was similar between genotypes after a high salt challenge (Flox: 3187±382, KO: 2744±291pg/day; n=8–10/group, p>0.05), suggesting that female mice are able to compensate for a loss of NOS1‐derived NO in the collecting duct. Additionally, we performed RT‐PCR on male and female renal vessels and found that unlike males, female CDNOS1KO mice have significantly elevated vascular endothelin 1 mRNA expression (Male‐ flox: 1.00±0.09, KO: 0.98±0.03; n=6/group, p>0.05; Female‐ flox: 1.00±0.18, KO: 1.75±0.24; n=5–6/group, p=0.03). In conclusion, female mice do not rely on collecting duct NOS1‐derived NO to maintain fluid‐electrolyte balance. We propose that female mice utilize endothelin‐1 and/or NO production in other renal segments. Support or Funding Information F31DK111067 to RSS, F31HL149235 to LSD, and P01HL136267, AHA 19SRG34930023 to JSP