Activation of endothelial BK_Ca channels causes pulmonary vasodilation

Background: Large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels cause hyperpolarization and can regulate vascular tone. In this study, we evaluated the effect of endothelial BK_Ca activation on pulmonary vascular tone. Methods: The presence of BK_Ca channels in lung microvascular endothelial cells (LMVEC) and rat lung tissue was confirmed by RT-PCR, immunoblotting and immunohistochemistry. Isolated pulmonary artery (PA) rings and isolated ventilated-perfused rat lungs were used to assay the effects of BK_Ca channel activation on endothelium-dependent vasodilation. Results: Immunoblotting and RT-PCR revealed the presence of BK_Ca channel α- and β₄-subunits in LMVEC. Immunohistochemical staining showed BK_Ca channel α-subunit expression in vascular endothelium in rat lungs. In arterial ring studies, BK_Ca channel activation by NS1619 enhanced endothelium-dependent vasodilation that was attenuated by tetraethylammonium and iberiotoxin. In addition, activation of BK_Ca channels by C-type natriuretic peptide caused endothelial-dependent vasodilation that was blocked by iberiotoxin, L-NAME, and lanthanum. Furthermore, BK_Ca activation by NS1619 caused a dose-dependent reduction in PA pressures that was attenuated by L-NAME. In vitro, BK_Ca channel activation in LMVEC caused hyperpolarization and increased NO production. Conclusions: Pulmonary endothelium expresses BK_Ca channels. Activation of endothelial BK_Ca channels causes hyperpolarization and NO mediated endothelium-dependent vasodilation in micro- and macrovasculature in the lung.