Hypoxia impairs nitrovasodilator-induced pulmonary vasodilation: role of Na-K-ATPase activity.

To elucidate the effect of hypoxia on nitrovasodilator-induced pulmonary vasodilation, we studied canine pulmonary arterial rings under isometric conditions in vitro. Exposure to hypoxia inhibited the relaxant responses of KCl-contracted tissues to sodium nitroprusside (SNP), so that the maximal relaxation (Emax) and the negative logarithm of molar concentration required to produce 50% relaxation (pD2) were decreased from 92 +/- 7 to 62 +/- 5% and from 5.8 +/- 0.2 to 4.7 +/- 0.3, respectively (means +/- SE, P < 0.01 for each). This effect was likewise observed when 8-bromoguanosine-3',5'-cyclic monophosphate was used as a relaxant. The impairment of SNP-induced relaxation of endothelium-denuded rings under hypoxia was abolished by ouabain or K(+)-free solution. Incubation with SNPincreased intracellular cGMP contents in a dose dependent manner, an effect that was not altered by hypoxia. SNP also increased ouabain-sensitive 86Rb uptake, and this effect was inhibited by hypoxia. These results suggest that hypoxia reduces nitrovasodilator-induced relaxation of pulmonary artery, probably through an inhibition of cGMP-dependent sarcolemmal Na-K-adenosine triphosphatase activity.