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Enhanced urinary sodium and potassium excretion in VAMP3 knockout mice
Author(s) -
Haque Mohammed Ziaul,
Ortiz Pablo Alfredo
Publication year - 2013
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.27.1_supplement.1115.26
Subject(s) - excretion , endocrinology , medicine , kidney , urinary system , blood pressure , homeostasis , renal function , biology , chemistry
Several members of the vesicle associated membrane proteins (VAMP) family are expressed in the kidney. VAMP3 is expressed in the apical membrane of the thick ascending limb (TAL) where it mediates NKCC2 trafficking to the apical membrane. Other transporters along the nephron segment may also be regulated by VAMP3 thereby influencing renal function. We hypothesized that VAMP3 is involved in maintaining renal Na excretion and thus blood pressure. To test our hypothesis we obtained homozygous VAMP3 knockout mice (KO) and measured systolic blood pressure (SBP) and urinary parameters using c57BL6 mice (WT) as controls. Urinary Na excretion was higher (325±25 vs 248±20 μmoles/day) as was K excretion (785±76 vs 645±27 μmoles/day) and urine volume (2.56±0.16 vs 1.95±0.19 ml/day) without a change in urinary creatinine. Body weight tended to be higher but not significantly so (27.2±0.6 vs 26.3 ±0.2 gram). After decreasing Na in the diet from 0.4 to 0.02% for 24 hours, Na excretion decreased in both strains. However, it remained elevated in KO (61±14 vs 38±3 μmoles/day). Baseline SBP was lower in KO mice compared to WT (KO: 101±3 vs WT: 115±3 mmHg). Feeding mice a low salt diet for 7 days did not further decrease SBP in VAMP3 KO (96±4 mmHg) but it decreased in WT (99±3 mmHg). Taken together our data suggest that VAMP3 maintains normal renal Na excretion and is involved in blood pressure homeostasis. This is the first phenotype observed in VAMP3 KO mice.