Role of Na+-K+-ATPase in Sodium Nitroprusside-Induced Relaxation of Pulmonary Artery under Hypoxia

Abstract

Background: The sodium pump (Na⁺-K⁺-ATPase) plays a part in the regulation of smooth muscle contractility, and alterations of enzyme activity by hypoxia could contribute to the mechanism of hypoxic pulmonary vasoconstriction. Objective: To determine the role of Na⁺-K⁺-ATPase in the sodium nitroprusside (SNP)-induced relaxation of pulmonary artery in hypoxia. Methods: Using isolated canine pulmonary arterial rings, we measured the relaxant responses of KCI-contracted tissues to SNP under hyperoxic (95% O₂, 5% O₂) and hypoxic conditions (5% O₂, 5% CO₂, 90% N₂) in vitro. Na⁺-K⁺-ATPase activity was assessed by measuring ouabain-sensitive ⁸⁶Rb uptake. Results: The SNP-induced relaxation was reduced under hypoxia, so that the maximal relaxation decreased from 80.1 ± 8.6 to 57.8 ± 6.8% (p < 0.01) and the concentration of SNP required to produce 50% relaxation increased from 1.9 ± 0.4 × 10^–6 to 2.6 ± 0.6 × 10^–5M (p < 0.01). Addition of ouabain, an Na⁺-K⁺-ATPase inhibitor, attenuated the relaxant response to SNP and this inhibition was still observed under hypoxia. Incubation of endothelium-denuded rings with SNP caused dose-dependent increases in intracellular cGMP levels and ouabain-sensitive ⁸⁶Rb uptake, and these effects were not significantly altered by hypoxia. Conclusion: These results suggest that sarcolemmal Na⁺-K⁺-ATPase activity may be implicated in the mechanism of nitrovasodilator-induced vasodilation of pulmonary artery and may still be functioning under hypoxia.