IN-VITRO HYPOXIA ON RAT PULMONARY-ARTERY - EFFECTS ON CONTRACTIONS TOSPASMOGENS AND ROLE OF K-ATP CHANNELS

The effect of in vitro hypoxia for 1 h on concentration-response curve s to vasoconstrictor spasmogens was examined in rat isolated pulmonary arteries. Hypoxia, like levcromakalim (K-ATP channel opener), did not affect contractions to endothelin-1 but attenuated contractions to U4 6619 ((1,5,5,)-hydroxy-11 alpha,9 alpha-epoxymethano) prosta 5Z, 13E-d ienoic acid; thromboxane-mimetic), angiotensin II, noradrenaline and 5 -hydroxytryptamine. The attenuation was prevented by glybenclamide. In pre-contracted arteries, subsequent exposure to hypoxia caused a resp onse consisting of four phases (transient relaxation due to endotheliu m-derived nitric oxide; transient contraction; slow relaxation; sustai ned contraction). Glybenclamide, if added before hypoxia, did not elim inate either of the relaxant phases but, if added during the sustained contractile phase, caused further contraction. We conclude that expos ure of pulmonary arteries to prolonged hypoxia causes K-ATP channels t o open, as in systemic arteries; this diminishes contractions to some, but not all, vasoconstrictor spasmogens. The data suggest that endoth elin-1, unlike other vasoconstrictors, would remain a highly effective pulmonary vasoconstrictor under severe hypoxic conditions.