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Upregulation of the thiazide‐sensitive sodium chloride cotransporter in the kidney is associated with the hypertension in D3 dopamine receptor heterozygous (D3 ‐/+) mice
Author(s) -
Wang Xiaoyan,
Escano Crisanto S,
Asico Laureano,
Jones John E,
Jose Pedro A
Publication year - 2009
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.23.1_supplement.605.13
Subject(s) - endocrinology , medicine , chemistry , dopamine receptor d3 , thiazide , aquaporin 2 , kidney , natriuresis , aldosterone , sodium , receptor , blood pressure , dopamine receptor , water channel , mechanical engineering , engineering , inlet , organic chemistry
D3 dopamine receptor (D3R) knockout (D3‐/‐) mice have hypertension related to an increased protein expression of thiazide‐sensitive sodium chloride cotransporter (NCC) in the renal distal convoluted tubule. D3R heterozygous mice (D3 ‐/+) are also hypertensive. To determine if a mechanism involved in the pathogenesis of hypertension in D3 ‐/+ is similar to that in D3‐/‐ mice, we measured renal NCC protein abundance in D3‐/+ and their wild type (D3+/+) littermates. On normal NaCl intake, blood pressure (BP, telemetry) was higher in D3‐/+ than in D3+/+ mice but body weight, serum electrolytes and urinary sodium excretion were similar. NCC protein expression in D3‐/+ mice was increased in the renal plasma membrane‐enriched (136±7) and intracellular‐vesicle enriched fractions (154±7) (% of D3+/+, n=6/group). To determine the role of the increased NCC expression in the hypertension of D3‐/+ mice, they were treated with hydrochlorothiazide (HTZ, 30 mg/Kg X 3 days, IP), a specific NCC inhibitor. There was a more than 2‐fold increase in HTZ‐induced natriuresis in D3‐/+ (19.2±3.0) relative to D3+/+ mice (8.1±2.3)(nEq/h, 6 hours post HTZ injection,n=5/group). BP decreased sooner (on day 2 in D3‐/+ mice and on day 3 in D3+/+ mice) and to a greater extent in D3‐/+ (21±2) than in D3+/+ mice (14±1)(mm Hg, n=4/group). We conclude that the hypertension of D3R deficient mice is associated with upregulation of the renal NCC.