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(Hypertension. 1999;33:504-510.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Selective Inhibition of the Renal Dopamine Subtype D_1A Receptor Induces Antinatriuresis in Conscious Rats

Zhi-Qin Wang; Robin A. Felder; Robert M. Carey

From the Departments of Medicine (Z.Q.W., R.M.C.) and Pathology (R.A.F.), University of Virginia Health Sciences Center, Charlottesville, Va.

Correspondence to Dr Robert M. Carey, Box 395, University of Virginia Health Sciences Center, Charlottesville, VA 22908. E-mail RMC4C{at}virginia.edu

Abstract—Both dopamine D₁-like (D_1A and D_1B) and D₂-like (D₂, D₃, and D₄) receptor subfamilies are present in the kidney. Blockade of the intrarenal D₁-like receptor family is associated with natriuresis and diuresis. Because the D_1A and D_1B receptor subtypes are not distinguishable by currently available dopaminergic agents, their functional role remains undefined. In the present study, the effect of selective inhibition of the renal D_1A receptor with phosphorothioated antisense oligodeoxynucleotide (AS-ODN) was investigated in conscious uninephrectomized rats. After renal interstitial administration of Texas red–labeled D_1A receptor AS-ODN, intense fluorescent signal was localized in the renal tubular epithelium and vasculature. In rats on normal salt intake, AS-ODN injected interstitially into the kidney reduced daily urinary sodium excretion (1.4±0.04 versus 0.8±0.2 mEq/d, n=5, P<0.05) and urine output (16.9±3.8 versus 12.5±3.6 mL/d, n=5, P<0.05). In rats on high sodium intake, continuous renal interstitial administration of D_1A receptor AS-ODN transiently decreased daily urinary sodium excretion (5.4±0.5 versus 4.2±0.3 mEq/d, n=7, P<0.01) and urine output (27.6±4.5 versus 18.1±1.8 mL/d, n=7, P<0.01). Neither vehicle nor sense oligodeoxynucleotide had significant effects. Systolic blood pressure remained unchanged. The renal D_1A receptor protein was significantly decreased by 35% and 46% at the end of the study in AS-ODN–treated rats on normal and high salt intake, respectively, whereas the D_1B receptor and ß-actin were not affected. These results provide the first direct evidence that the renal D_1A receptor subtype plays an important role in the control of sodium excretion.

Key Words: oligonucleotides, antisense • receptors, dopamine • kidney • sodium excretion

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