Role of Na+-K+-ATPase in sodium nitroprusside-induced relaxation of pulmonary artery under hypoxia

Background: The sodium pump (Na+-K+-ATPase) plays a part in the regulation of smooth muscle contractility, and alterations of enzyme activity by hypox ia could contribute to the mechanism of hypoxic pulmonary vasoconstriction, Objective: To determine the role of Na+-K+- ATPase in the sodium nitroprus side (SNP)-induced relaxation of pulmonary artery in hypoxia. Methods: Usin g isolated canine pulmonary arterial rings, we measured the relaxant respon ses of KCI-contracted tissues to SNP under hyperoxic (95% O-2, 5% O-2) and hypoxic conditions (5% O-2, 5% CO2, 90% N-2) in vitro. Na+-K+-ATPase activi ty was assessed by measuring ouabain-sensitive Rb-86 up take. Results:The S NP-induced relaxation was reduced under hypoxia, so that the maximal relaxa tion decreased from 80.1 +/- 8.6 to 57.8 +/- 6.8% (p <0.01) and the concent ration of SNP required to produce 50% relaxation increased from 1.9 +/- 0.4 x 10(-6) to 2.6 +/- 0.6 x 10(-5) M (p < 0.01). Addition of ouabain, an Na-K+-AtPase inhibitor, attenuated the relaxant response to SNP and this inhi bition was still observed under hypoxia. Incubation of endothelium-denuded rings with SNP caused dose-dependent increases in intracellular cGMP levels and ouabain-sensitive Rb-86 uptake, and these effects were not significant ly altered by hypoxia. Conclusion: These results suggest that sarcolemmal N a+-K+-ATPase activity may be implicated in the mechanism of nitrovasodilato r-induced vasodilation of pulmonary artery and may still be functioning und er hypoxia. Copyright (C) 2001 S. Karger AG, Basel.