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(Circulation Research. 2006;99:494.)
© 2006 American Heart Association, Inc.

Molecular Medicine

Activation of D₃ Dopamine Receptor Decreases Angiotensin II Type 1 Receptor Expression in Rat Renal Proximal Tubule Cells

Chunyu Zeng, Yan Liu, Zheng Wang, Duofen He, Lan Huang, Peiying Yu, Shaopeng Zheng, John E. Jones, Laureano D. Asico, Ulrich Hopfer, Gilbert M. Eisner, Robin A. Felder, Pedro A. Jose

From the Department of Cardiology (C.Z., Y.L., D.H.), Daping Hospital, and Xinqiao Hospital (L.H.), Third Military Medical University, Chongqing, People’s Republic of China; Departments of Pediatrics (Z.W., P.Y., S.Z., J.E.J., L.D.A., G.M.E., P.A.J.), Physiology and Biophysics (P.A.J.), and Internal Medicine (G.M.E.), Georgetown University Medical Center, Washington DC; Department of Physiology and Biophysics (U.H.), Case Western Reserve School of Medicine, Cleveland, Ohio; and Department of Pathology (R.A.F.), University of Virginia Health Sciences Center, Charlottesville.

Correspondence to Dr Chunyu Zeng, Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, People’s Republic of China. E-mail cyzeng1{at}hotmail.com

The dopaminergic and renin angiotensin systems interact to regulate blood pressure. Disruption of the D₃ dopamine receptor gene in mice produces renin-dependent hypertension. In rats, D₂-like receptors reduce angiotensin II binding sites in renal proximal tubules (RPTs). Because the major D₂-like receptor in RPTs is the D₃ receptor, we examined whether D₃ receptors regulate angiotensin II type 1 (AT₁) receptors in rat RPT cells. The effect of D₃ receptors on AT₁ receptors was studied in vitro and in vivo. The D₃ receptor agonist PD128907 decreased AT₁ receptor protein and mRNA in WKY RPT cells and increased it in SHR cells. PD128907 increased D₃ receptors in WKY cells but had no effect in SHR cells. D₃/AT₁ receptors colocalized in RPT cells; D₃ receptor stimulation decreased the percent amount of D₃ receptors that coimmunoprecipitated with AT₁ receptors to a greater extent in WKY than in SHR cells. However, D₃ receptor stimulation did not change the percent amount of AT₁ receptors that coimmunoprecipitated with D₃ receptors in WKY cells and markedly decreased the coimmunoprecipitation in SHR cells. The D₃ receptor also regulated the AT₁ receptor in vivo because AT₁ receptor expression was increased in kidneys of D₃ receptor–null mice compared with wild type littermates. D₃ receptors may regulate AT₁ receptor function by direct interaction with and regulation of AT₁ receptor expression. One mechanism of hypertension may be related to increased renal expression of AT₁ receptors due decreased D₃ receptor regulation.

Key Words: AT₁ receptor • D₃ receptor • renal proximal tubule cells • hypertension

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