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(Hypertension. 2003;42:787.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Perturbation of D₁ Dopamine and AT₁ Receptor Interaction in Spontaneously Hypertensive Rats

Chunyu Zeng; Yingjin Luo; Laureano D. Asico; Ulrich Hopfer; Gilbert M. Eisner; Robin A. Felder; Pedro A. Jose

From the Departments of Pediatrics (C.Z., Y.L., 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; the Department of Physiology (U.H.), Case Western Reserve School of Medicine, Cleveland, Ohio; the Department of Pathology (R.A.F.), Virginia University for the Health Sciences, Charlottesville, Va; and the Department of Cardiology (C.Z.), Daping Hospital, Third Military Medical University, Chongqing, Peoples Republic of China.

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

The dopaminergic and renin-angiotensin systems interact to regulate blood pressure. Because this interaction may be perturbed in genetic hypertension, we studied D₁ dopamine and AT₁ angiotensin receptors in immortalized renal proximal tubule (RPT) and A10 aortic vascular smooth muscle cells. In normotensive Wistar-Kyoto (WKY) rats, the D₁-like agonist fenoldopam increased D₁ receptors but decreased AT₁ receptors. These effects were blocked by the D₁-like antagonist SCH 23390 (10^-7 mol/L per 24 hours). In spontaneously hypertensive rat (SHR) RPT cells, fenoldopam also decreased AT₁ receptors but no longer stimulated D₁ receptor expression. Basal levels of AT₁/D₁ receptor coimmunoprecipitation were greater in WKY RPT cells (29±2 density units, DU) than in SHR RPT cells (21±2 DU, n=7 per group, P<0.05). The coimmunoprecipitation of D₁ and AT₁ receptors was increased by fenoldopam (10^-7 mol/L per 24 hours) in WKY RPT cells but decreased in SHR RPT cells. The effects of fenoldopam in RPT cells from WKY rats were similar in aortic vascular smooth muscle cells from normotensive BD IX rats, that is, fenoldopam decreased AT₁ receptors and increased D₁ receptors. Our studies show differential regulation of the expression of D₁ and AT₁ receptors in RPT cells from WKY and SHR. This regulation and D₁/AT₁ receptor interaction are different in RPT cells of WKY and SHR. An altered interaction of D₁ and AT₁ receptors may play a role in the impaired sodium excretion and enhanced vasoconstriction in hypertension.

Key Words: hypertension, essential • receptors, angiotensin II • dopamine • kidney • muscle, smooth, vascular

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