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Upregulation of NHE3 in renal proximal tubule is associated with hGRK4 486V‐promoted salt sensitivity in transgenic mice
Author(s) -
Wang Xiaoyan,
Wang Zheng,
Asico Laureano D,
Escano Crisanto,
Jose Pedro A
Publication year - 2008
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.22.1_supplement.969.29
Subject(s) - natriuresis , endocrinology , medicine , chemistry , epithelial sodium channel , sodium , kidney , excretion , genetically modified mouse , proximal tubule , downregulation and upregulation , homeostasis , transgene , biology , biochemistry , organic chemistry , gene
Salt‐sensitive hypertension in humans is associated with variants of GRK4. hGRK4γ 486V causes salt‐resistant mice (25% SJL/J, 75% CB57BL/6J) to become salt‐sensitive. In current studies, we measured blood pressure (BP), urinary sodium excretion (UNaV), and renal sodium transporters in the 486V transgenic mice (486V) and non‐transgenic littermates (NT) maintained on normal (0.9%, NS) or high (6%, HS) NaCl diet for 3 weeks. BPs were increased in 486V by HS but not affected in NT while UNaV was similar in both mouse strains on NS and HS, suggesting a blunted pressure‐natriuresis response. On NS, 486V mice had lower protein abundance of NHE3 (65±3, NT set as 100%) and αENaC (75±9) but greater abundance of NaPi2 (277±18), γENaC (164±34), and αNKA (196±28); No difference was found in NKCC2, NCC and βENaC. HS decreased NHE3 (47±6) and αENaC (67±8) only in NT, the expected normal response in salt‐resistant mice. HS did not decrease the other sodium transporters in either mouse strain. Because the activity of plasma membrane transporters is better reflected on the expression at the plasma membrane, we measured NHE3 in renal brush border membranes (BBM). On NS, BBM NHE3 was similar in 486V and NT mice (110±13 vs 100±27, respectively). On HS, it was dramatically increased in 486V mice (230±41) but not altered in NT mice (118±24). Our findings suggest that increased sodium transport in the proximal tubule may contribute to the blunted pressure‐natriuresis and salt‐sensitive hypertension in hGRK4γ 486V transgenic mice.