SEGMENTAL PULMONARY VASCULAR-RESPONSES TO ATP IN RAT LUNGS - ROLE OF NITRIC-OXIDE

ATP exhibits vascular presser and depressor responses in a dose- and t one-dependent manner. The vascular site of ATP-induced contraction or dilation has not previously been characterized. Using the vascular occ lusion technique, we investigated the effects of ATP in isolated rat l ungs perfused with autologous blood (hematocrit = 20%) and described i ts action during resting and elevated tone in terms of changes in resi stances of the small and large arteries and veins. During resting tone , ATP (10(-5) M) caused contraction primarily in the small arteries an d, to some extent, in the small veins, suggesting that P-2x purinocept ors are present in these small vessels. During hypoxia, ATP caused dil ation primarily in the small arteries, suggesting that P-2y purinocept ors are predominant in small arteries. During U-46619-induced contract ion, which occurred evenly throughout the four segments, ATP caused di lation in the large arteries and veins but not in the small arteries a nd veins. After treatment with N-omega-nitro-L-arginine to inhibit nit ric 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 resp onses were not affected significantly by indomethacin. in conclusion, the results indicate that the effects of ATP on the pulmonary vasculat ure are primarily due to P-2x and P-2y purinoceptors in the small arte ries. Contribution of these purinoceptors in other vessels to changes in total vascular resistance in rat lung was minor.