Measurements of isometric tensions of rat aortic rings revealed the fact that when aortic rings with intact endothelium were precontracted (preconditioned) for 20 min by the ₁-adrenergic agonist phenylephrine (10 µM), the tonic level of subsequent contraction by the same agonist was depressed and/or declined regardless of the presence or absence of endothelium during the second contraction. The removal of endothelium before preconditioning showed no such phenomenon. With the use of specific blockers, involvements of adenosine or of ATP-sensitive K⁺ (K_ATP) channels during preconditioning or second contraction, respectively, were evaluated. Actions of nitric oxide synthase, cyclooxygenase, P₂ ATP purinoceptors, or K_ATP channels during preconditioning appear not to be involved. Exogenous adenosine (up to 100 µM) without endothelium could mimic the preconditioning; however, contractile preconditioning by phenylephrine, mechanical stretching, or activation of protein kinase C needed to be done. The release of adenosine and adenine nucleotides from aortic rings was augmented by phenylephrine or by mechanical stretching of the rings with intact endothelium. Our results suggest that during vasocontraction, endothelium-derived adenosine acquires an ability to protect vascular tone against subsequent repeated contractions by mediating a delayed, possibly indirect, opening of K_ATP channels.