The vasodilator effect of adenosine on the contraction induced by phenylephrine, an alpha 1-adrenergic receptor agonist, was investigated in the isolated rat aorta. We found that the effect of adenosine was greater in intact aortas than in endothelium-denuded preparations. Denuding caused a parallel shift of the dose-response curve of adenosine to the right by a factor of five in comparison with intact aorta. This finding indicates that the relaxing effect of adenosine is partially endothelium-dependent in rat aorta. The mechanism of action of adenosine on vascular smooth muscle was also investigated in receptor-mediated and voltage-dependent calcium influx experiments performed with the addition of phenylephrine and high potassium concentrations, respectively. Although adenosine significantly inhibited only the tonic phase of the contraction induced by phenylephrine (10(-5) M), it did so to both the fast and slow phases of the contraction produced by high potassium concentrations (75 mM) with no preferential difference. In comparison to verapamil, a calcium entry blocker, adenosine behaved in a manner similar to that of verapamil in counteracting the constriction induced by either phenylephrine or potassium. We conclude that the vasodilator effect of adenosine is partially endothelium-dependent and that the mechanism of this effect may involve the inhibition of calcium influx and the release of an endothelium-derived relaxing factor.