ATP exhibits vascular pressor and depressor responses in a dose-and tone-dependent manner. The vascular site of ATPinduced contraction or dilation has not previously been characterized. Using the vascular occlusion technique, we investigated the effects of ATP in isolated rat lungs perfused with autologous blood (hematocrit 5 20%) and described its action during resting and elevated tone in terms of changes in resistances of the small and large arteries and veins. During resting tone, ATP (10

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... M) caused contraction primarily in the small arteries and, to some extent, in the small veins, suggesting that P 2x purinoceptors are present in these small vessels. During hypoxia, ATP caused dilation primarily in the small arteries, suggesting that P 2y purinoceptors are predominant in small arteries. During U-46619-induced contraction, which occurred evenly throughout the four segments, ATP caused dilation in the large arteries and veins but not in the small arteries and veins. After treatment with N v -nitro-Larginine to inhibit nitric oxide synthesis, ATP-induced contraction was potentiated, and its dilatory effects during hypoxia were attenuated. The action of ATP was independent of prostanoids, because its constrictor and dilatory responses were not affected significantly by indomethacin. In conclusion, the results indicate that the effects of ATP on the pulmonary vasculature are primarily due to P 2x and P 2y purinoceptors in the small arteries. Contribution of these purinoceptors in other vessels to changes in total vascular resistance in rat lung was minor.