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

Document Type

Journal Article

Publication Date

3-1-2004

Journal

Hypertension

Volume

43

Issue

3

DOI

10.1161/01.HYP.0000118958.27649.6f

Keywords

Arteries; Blood pressure; Dopamine; Receptor

Abstract

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). D 1 and D3 receptors physically interacted with each other because fenoldopam (10-7 M/24 h) increased D1/D 3 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 D 3 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 D 1 and D3 receptors may be involved in the regulation of blood pressure.

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