Activation of endothelial BKCa channels causes pulmonary vasodilation

Background: Large-conductance Ca2+-activated K+ (BKCa) channels cause hyperpolarization and can regulate vascular tone. In this study, we evaluated the effect of endothelial BKCa activation on pulmonary vascular tone. Methods: The presence of BKCa 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 BKCa channel activation on endothelium-dependent vasodilation. Results: Immunoblotting and RT-PCR revealed the presence of BKCa channel alpha- and beta(4)-subunits in LMVEC. Immunohistochemical staining showed BKCa channel alpha-subunit expression in vascular endothelium in rat lungs. In arterial ring studies, BKCa channel activation by NS1619 enhanced endothelium-dependent vasodilation that was attenuated by tetraethylammonium and iberiotoxin. In addition, activation of BKCa channels by C-type natriuretic peptide caused endothelial-dependent vasodilation that was blocked by iberiotoxin, L-NAME, and lanthanum. Furthermore. BKCa activation by NS1619 caused a dose-dependent reduction in PA pressures that was attenuated by L-NAME. In vitro, BKCa channel activation in LMVEC caused hyperpolarization and increased NO production. Conclusions: Pulmonary endothelium expresses BKCa channels. Activation of endothelial BKCa channels causes hyperpolarization and NO mediated endothelium-dependent vasodilation in micro- and macrovasculature in the lung. Published by Elsevier Inc.