Effects of a platelet-released, naturally occurring nucleotide, adenosine 5'-tetraphosphate (ATPP) on vascular tone were analyzed in the isolated rat aorta. Under resting tension ATPP (1 approximately 100 µM) elicited concentration-dependent contractions in endothelium-intact aortic rings in contrast to the concentration-dependent relaxation with ATP. In endothelium-denuded aortic rings, ATPP induced contraction, as ATP did, but with a greater potency. α, β-methylene ATP (APCPP 50 µM), a P_2x-purinoceptor antagonist, significantly inhibited ATPP- as well as ATP-induced contractions in the endothelium-denuded preparations suggesting that ATPP acts via P_2x-purinoceptors. ATPP (10 approximately 100 µM) relaxed precontracted aortic rings with an intact endothelium in a concentration-dependent manner. This effect of ATPP was 3.7 fold less potent than that of ATP. However, after P_2x-purinoceptor blockade, the effect became identical between the two nucleotides. Reactive blue 2, a selective antagonist of P_2x-purinoceptors, significantly attenuated the ATPP-induced relaxation with no change in the ATP-induced relaxation. These results indicated that the rat aortic endothelium contains heterogeneous populations of P₂-purinoceptors (possibly P_2y and nucleotide receptors). Since ATPP shows dual effects depending upon the vascular tension, it may play a significant role in the physiological regulation of vascular tone.