Published Online
on January 19, 2004

A more recent version of this article appeared on March 1, 2004

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Submitted on September 2, 2003
Revised on September 30, 2003

Aberrant D₁ and D₃ Dopamine Receptor Transregulation in Hypertension

Chunyu Zeng^*; Dan Wang; Laureano D. Asico; William J. Welch; Christopher S. Wilcox; Ulrich Hopfer; Gilbert M. Eisner; Robin A. Felder; and Pedro A. Jose

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

^* To whom correspondence should be addressed. E-mail: cyzeng1{at}hotmail.com.

Abstract--Dopamine plays a role in the regulation of blood pressure by inhibition of sodium transport in renal proximal tubules (RPTs) and relaxation of vascular smooth muscles. Because dopamine receptors can regulate and interact with each other, we studied the interaction of D₁ and D₃ receptors in immortalized RPT cells and mesenteric arteries from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs), and in human coronary artery smooth muscle cells (CASMCs). In WKY rats, the D₁-like agonist, fenoldopam, increased D₃ receptor protein in a time-dependent and concentration-dependent manner (EC₅₀=4.5x10^-9 M, t_1/2=15.8 hours). In SHRs, fenoldopam (10^-5 M) actually decreased the expression of D₃ receptors. D₁ and D₃ receptor co-immunoprecipitation was increased by fenoldopam (10^-7 M/24 h) in WKY rats but not in SHRs. The effects of fenoldopam in CASMCs were similar as those in WKY RPT cells (ie, fenoldopam increased D₁ and D₃ receptor proteins). Both D₃ (PD128907, Emax=80%±6%, pED₅₀=5±0.1) and D₁-like receptor (fenoldopam, Emax=81%±8%, pED₅₀=5±0.2, n=12) agonists relaxed mesenteric arterial rings. Co-stimulation of D₁ and D₃ receptors led to additive vasorelaxation in WKY rats, but not in SHRs. D₁ and D₃ receptors interact differently in WKY and SHRs. Altered interactions between D₁ and D₃ receptors may play a role in the pathogenesis of genetic hypertension, including human hypertension, because these receptors also interact in human vascular smooth muscle cells.

Key words: receptors • dopamine • rats • hypertension • normotension • kidney • vascular smooth muscle

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