Upregulation of renal sodium transporters in D5 dopamine receptor-deficient mice
AT1R blockade; Dopamine; Dopamine receptor; Hypertension; Knockout mouse; Sodium excretion; Sodium transporters
D5 dopamine receptor (D5R)-deficient (D 5-/-) 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 D 5-/- 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. © 2010 American Heart Association, Inc.
Wang, X., Luo, Y., Escano, C., Yang, Z., Asico, L., Li, H., Jones, J., Armando, I., Lu, Q., Sibley, D., Eisner, G., & Jose, P. (2010). Upregulation of renal sodium transporters in D5 dopamine receptor-deficient mice. Hypertension, 55 (6). http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.148643