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(Hypertension. 2004;43:673.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Dopamine D₁ Receptor Augmentation of D₃ Receptor Action in Rat Aortic or Mesenteric Vascular Smooth Muscles

Chunyu Zeng; Dan Wang; Zhiwei Yang; Zheng Wang; Lareano D. Asico; Christopher S. Wilcox; Gilbert M. Eisner; William J. Welch; Robin A. Felder; Pedro A. Jose

From Department of Pediatrics (C.Z., Z.Y., Z.W., L.D.A., G.M.E., P.A.J.), Physiology and Biophysics (Z.Y., P.A.J.), and Internal Medicine (G.M.E.), Division of Nephrology and Hypertension and Center for Hypertension and Renal Disease Research (D.W., C.S.W., W.J.W.), Georgetown University Medical Center, Washington, DC; Department of Pathology (R.A.F.), Virginia University for the Health Sciences, Charlottesville; Department of Cardiology (C.Z.), Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China.

Correspondence to Dr Chunyu Zeng, Department of Pediatrics, PHC-2 Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20007. E-mail cyzeng1{at}hotmail.com

Dopamine is an important modulator of blood pressure, in part, by regulating vascular resistance. To test the hypothesis that D₁ and D₃ receptors interact in vascular smooth muscle cells, we studied A10 cells, a rat aortic smooth muscle cell line, and rat mesenteric arteries that express both dopamine receptor subtypes. Fenoldopam, a D₁-like receptor agonist, increased both D₁ and D₃ receptor protein in a time-dependent and a concentration-dependent manner in A10 cells. The effect of fenoldopam was specific because a D₁-like receptor antagonist, SCH23390 (10^-7 M/24 h), completely blocked the stimulatory effect of fenoldopam (10^-7 M/24 h) (D₃ receptor: control=21±1 density units [DU]); SCH23390=23±2 DU; fenoldopam=33±2 DU; fenoldopam+SCH23390=23±2 DU; n=10). D₁ and D₃ receptors physically interacted with each other because fenoldopam (10^-7 M/24 h) increased D₁/D₃ receptor coimmunoprecipitation (35±5 versus 65±5 DU; n=8). A D₃ receptor agonist, PD128907, relaxed mesenteric arterial rings independent of the endothelium, effects that were blocked by a D₃ receptor antagonist, U99194A. Costimulation of D₁ and D₃ receptors led to additive vasorelaxation. We conclude that the D₁ receptor regulates the D₃ receptor by physical interaction and receptor expression. D₁ receptor stimulation augments D₃ receptor vasorelaxant effects. An interaction of D₁ and D₃ receptors may be involved in the regulation of blood pressure.

Key Words: receptor • dopamine • arteries • blood pressure

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