Upregulation of Renal Sodium Transporters in D5 Dopamine Receptor–Deficient Mice

D5 dopamine receptor (D5R)-deficient (D5) mice have hypertension that is aggravated by an increase in sodium intake. The present experiments were designed to test the hypothesis that a dysregulation of renal sodium transporters is related to the salt sensitivity in D5 mice. D5R was expressed in the renal proximal tubule, thick ascending limb, distal convoluted tubule, and cortical and outer medullary collecting ducts in D5 mice. On a control Na diet, renal protein expressions of NKCC2 (sodium-potassium-2 chloride cotransporter), sodium chloride cotransporter, and α and γ subunits of the epithelial sodium channel were greater in D5 than in D5 mice. Renal renin abundance and urine aldosterone levels were similar but renal angiotensin II type 1 receptor (AT1R) protein expression was increased in D5 mice. An elevated Na diet increased further the elevated blood pressure of D5 mice but did not affect the normal blood pressure of D5 mice. The increased levels of NKCC2, sodium chloride cotransporter, and α and γ subunits of the epithelial sodium channel persisted with the elevated Na diet and unaffected by chronic AT1R blockade (losartan) in D5 mice. The expressions of proximal sodium transporters NHE3 (sodium hydrogen exchanger type 3) and NaPi2 (sodium phosphate cotransporter type 2) were increased by the elevated Na diet in D5 mice; the increased expression of NHE3 but not NaPi2 was abolished by AT1R blockade. Our findings suggest that the increased protein expression of sodium transporters/channels in distal nephron segments may be the direct consequence of the disruption of D5R, independent of the renin–angiotensin aldosterone system.