Upregulation of renal sodium transporters in D5 dopamine receptor-deficient mice.
D(5) dopamine receptor (D(5)R)-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 D(5)(-/-) mice. D(5)R was expressed in the renal proximal tubule, thick ascending limb, distal convoluted tubule, and cortical and outer medullary collecting ducts in D(5)(+/+) mice. On a control Na(+) diet, renal protein expressions of NKCC2 (sodium-potassium-2 chloride cotransporter), sodium chloride cotransporter, and alpha and gamma subunits of the epithelial sodium channel were greater in D(5)(-/-) than in D(5)(+/+) mice. Renal renin abundance and urine aldosterone levels were similar but renal angiotensin II type 1 receptor (AT(1)R) protein expression was increased in D(5)(-/-) mice. An elevated Na(+) diet increased further the elevated blood pressure of D(5)(-/-) mice but did not affect the normal blood pressure of D(5)(+/+) mice. The increased levels of NKCC2, sodium chloride cotransporter, and alpha and gamma subunits of the epithelial sodium channel persisted with the elevated Na(+) diet and unaffected by chronic AT(1)R blockade (losartan) in D(5)(-/-) 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 AT(1)R 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 D(5)R, independent of the renin-angiotensin aldosterone system.
Wang
Xiaoyan
X
Center for Molecular Physiology Research, Children's National Medical Center, Washington, DC 20010, USA. xwang@cnmc.org
Luo
Yingjin
Y
Escano
Crisanto S
CS
Yang
Zhiwei
Z
Asico
Laureano
L
Li
Hewang
H
Jones
John E
JE
Armando
Ines
I
Lu
Quansheng
Q
Sibley
David R
DR
Eisner
Gilbert M
GM
Jose
Pedro A
PA
D000704:Analysis of Variance; D000818:Animals; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011336:Probability; D011897:Random Allocation; D050641:Receptors, Dopamine D5 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015222:Sodium Channels / Q000502:physiology; D049992:Sodium Chloride Symporters / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D015222:Sodium Channels; D049992:Sodium Chloride Symporters; D028021:Sodium-Potassium-Chloride Symporters; D050641:Receptors, Dopamine D5; D019808:Losartan
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