Format

Send to

Choose Destination
Vascul Pharmacol. 2010 Sep-Oct;53(3-4):122-9. doi: 10.1016/j.vph.2010.05.001. Epub 2010 May 12.

Activation of endothelial BKCa channels causes pulmonary vasodilation.

Author information

1
Vascular Research Laboratory, Providence VA Medical Center, Providence, RI 02908, USA.

Abstract

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.

PMID:
20470901
DOI:
10.1016/j.vph.2010.05.001
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center