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Increased renal sodium transporters are associated with hypertension in D4 dopamine receptor deficient mice
Author(s) -
wang xiaoyan,
Luo Yingjin,
Asico Laureano,
Jones John E.,
Escano Crisanto S.,
Jose Pedro A
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.21.6.a1366-d
We have reported that the disruption of the D4 dopamine receptor produces angiotensin type 1 receptor (AT1R)‐dependent hypertension. To understand further the mechanism of hypertension in D4 receptor deficient (D4−/−) mice, we checked the protein abundance of sodium transporters in the kidney. D4−/− and D4 +/+ littermates (n=4–6) were placed in metabolic cages with ration feeding on normal salt diet (0.8% NaCl) for 10 days. Femoral arterial systolic and diastolic blood pressures (SBP, DBP, mm Hg) under anesthesia confirmed the hypertension in D4−/− mice (D4−/−: SBP = 119+/−2, DBP = 83+/−1; D4+/+: SBP = 101+/−1, DBP = 74+/−2). There was no difference in urinary aldosterone concentration between D4−/− and D4+/+ mice. There was a small but significant increase in NHE3 protein (immunoblotting) in D4 −/− mice compared to D4+/+ mice. NKCC2 and NCC protein abundance was greatly increased in D4−/− (NKCC: 199+/−30%; NCC: 223+/−35% respectively) while the protein abundance of NaKATPase and the three subunits of ENaC was similar in the two strains. Immunocytochemistry revealed denser staining of NKCC2 and NCC at the apical membranes of the thick ascending limb and distal convoluted tubule, respectively in D4−/− mice compared to D4+/+ mice. The upregulation of renal sodium transporters, independent of aldosterone, may be a mechanism for the sodium retention and development of hypertension in D4−/− mice.