Abstract—Dopamine is an important modulator of blood pressure, in part, by regulating vascular resistance. To test the hypothesis that D1and D3receptors 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 D1and D3receptor 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 (10−7M/24 h), completely blocked the stimulatory effect of fenoldopam (10−7M/24 h) (D3receptor: control=21±1 density units [DU]); SCH23390=23±2 DU; fenoldopam=33±2 DU; fenoldopam+SCH23390=23±2 DU; n=10). D1and D3receptors physically interacted with each other because fenoldopam (10−7M/24 h) increased D1/D3receptor coimmunoprecipitation (35±5 versus 65±5 DU; n=8). A D3receptor agonist, PD128907, relaxed mesenteric arterial rings independent of the endothelium, effects that were blocked by a D3receptor antagonist, U99194A. Costimulation of D1and D3receptors led to additive vasorelaxation. We conclude that the D1receptor regulates the D3receptor by physical interaction and receptor expression. D1receptor stimulation augments D3receptor vasorelaxant effects. An interaction of D1and D3receptors may be involved in the regulation of blood pressure.