Expression of BK Ca channels in human pulmonary arteries: Relationship with remodeling and hypoxic pulmonary vasoconstriction

Abstract

Background Potassium channels are important in pulmonary circulation because they have been closely related to hypoxic pulmonary vasoconstriction (HPV). The objective of the study was to determine whether structural changes in pulmonary arteries (PA), such as those observed in patients with chronic obstructive pulmonary disease (COPD), might be associated with changes in the mRNA expression of both BK Ca and K V channels and their potential relationship with HPV. Methods PA (about 1.5 mm in diameter) were obtained from 16 patients who underwent resective lung surgery. Intimal thickening was evaluated morphometrically. mRNA expression of BK Ca, K V1.2, K V1.5, K V2.1 and K V3.1 was evaluated by RT-PCR in PA homogenates. Endothelial function and HPV were assessed in vitro in isolated PA using an organ bath. Results Intimal enlargement was closely associated with an increase in the expression of BK Ca channel ( r = 0.57, p < 0.05). Pulmonary arteries incubated with charybdotoxin, a BK Ca channel blocking agent, showed lower response to endothelium-dependent vasodilators indicating its contribution to reduce vascular tone. Pulmonary arteries with more pronounced responses to hypoxia were those with greater gene expression of BK Ca channels, suggesting a potential role in attenuating HPV ( r = 0.52, p < 0.05). No changes in the expression of K V channels were found in remodeled arteries. Conclusions Structural changes of PA in COPD could alter the response to hypoxia due to changes in BK Ca potassium channel distribution. Since BK Ca channels contribute to diminish vascular tone, their increased expression in remodeled PA might play a role in attenuating HPV.