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 Ca2+ 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+–Ca2+ exchanger with Ni2+ (10−3M) or the L-type Ca2+ channel with nimodipine (10−8M) dramatically attenuated KCl-induced contraction under hypoxia. Furthermore, prolonged hypoxia significantly reduced Na+, K+-ATPase activity and increased [Ca2+]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 [Ca2+]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.