Activation of endothelial BKCa channels causes pulmonary vasodilation.
BACKGROUND
Large-conductance Ca(2+)-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 alpha- and beta(4)-subunits in LMVEC. Immunohistochemical staining showed BK(Ca) channel alpha-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.
Vang
Alexander
A
Vascular Research Laboratory, Providence VA Medical Center, Providence, RI 02908, USA.
Mazer
Jeffrey
J
Casserly
Brian
B
Choudhary
Gaurav
G
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007811:Lanthanum / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D001562:Benzimidazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D014665:Vasodilator Agents; D020098:Natriuretic Peptide, C-Type; C086491:NS 1619; D009569:Nitric Oxide; D019789:Tetraethylammonium; D007811:Lanthanum; C064719:iberiotoxin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester