Activation of endothelial BKCa channels causes pulmonary vasodilation

Abstract

BackgroundLarge-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. MethodsThe 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. ResultsImmunoblotting and RT-PCR revealed the presence of BKCa channel α- and β4-subunits in LMVEC. Immunohistochemical staining showed BKCa channel α-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. ConclusionsPulmonary endothelium expresses BKCa channels. Activation of endothelial BKCa channels causes hyperpolarization and NO mediated endothelium-dependent vasodilation in micro- and macrovasculature in the lung.