The role of Na+, K+-ATPase in the hypoxic vasoconstriction in isolated rat basilar artery

Hypoxia-induced cerebrovascular dysfunction is a key factor in the occurrence and the development of cerebral ischemia. Na⁺, K⁺-ATPase affects the regulation of intracellular Ca^2 + concentration and plays an important role in vascular smooth muscle function. However, the potential role of Na⁺, K⁺-ATPase in hypoxia-induced cerebrovascular dysfunction is unknown. In this study, we found that the KCl-induced contraction under hypoxia in rat endothelium-intact basilar arteries is similar to that of denuded arteries, suggesting that hypoxia may cause smooth muscle cell (SMC)-dependent vasoconstriction in the basilar artery. The Na⁺, K⁺–ATPase activity of the isolated basilar artery with or without endothelium significantly reduced with prolonged hypoxia. Blocking the Na⁺–Ca^2 + exchanger with Ni^2 + (10^? 3 M) or the L-type Ca^2 + channel with nimodipine (10^? 8 M) dramatically attenuated KCl-induced contraction under hypoxia. Furthermore, prolonged hypoxia significantly reduced Na⁺, K⁺-ATPase activity and increased Ca^2 +]_i in cultured rat basilar artery SMCs. Hypoxia reduced the protein and mRNA expression of the α₂ isoform of Na⁺, K⁺-ATPase in SMCs in vitro. We used a low concentration of the Na⁺, K⁺-ATPase inhibitor ouabain, which possesses a high affinity for the α₂ isoform. The contractile response in the rat basilar artery under hypoxia was partly inhibited by ouabain pretreatment. The decreased Na⁺, K⁺-ATPase activity in isolated basilar artery and the increased Ca^2 +]_i in SMCs induced by hypoxia were partly inhibited by pretreatment with a low concentration of ouabain. These results suggest that hypoxia may educe Na⁺, K⁺-ATPase activity in SMCs through the α₂ isoform contributing to vasoconstriction in the rat basilar artery.