TY - JOUR
T1 - Activation of endothelial BKCa channels causes pulmonary vasodilation
AU - Vang, Alexander
AU - Mazer, Jeffrey
AU - Casserly, Brian
AU - Choudhary, Gaurav
N1 - Published by Elsevier Inc.
PY - 2010/9
Y1 - 2010/9
N2 - 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 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. 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.
AB - 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 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. 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.
KW - Endothelial cells
KW - Large-conductance calcium activated potassium channel
KW - Lung
KW - Vasodilation
UR - http://www.scopus.com/inward/record.url?scp=77956182127&partnerID=8YFLogxK
U2 - 10.1016/j.vph.2010.05.001
DO - 10.1016/j.vph.2010.05.001
M3 - Article
C2 - 20470901
AN - SCOPUS:77956182127
SN - 1537-1891
VL - 53
SP - 122
EP - 129
JO - Vascular Pharmacology
JF - Vascular Pharmacology
IS - 3-4
ER -