| Autor: |
Olivencia MA; Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain., Villegas-Esguevillas M; Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain., Sancho M; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain.; Department of Physiology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain., Barreira B; Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain., Paternoster E; Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain., Adão R; Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain., Larriba MJ; Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28029 Madrid, Spain.; Ciber Cáncer (CIBERONC), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria del Hospital Universitario La Paz (IdiPAZ), 28029 Madrid, Spain., Cogolludo A; Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain., Perez-Vizcaino F; Department of Pharmacology and Toxicology, School of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.; Ciber Enfermedades Respiratorias (CIBERES), 28029 Madrid, Spain.; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28009 Madrid, Spain. |
| Abstrakt: |
Recent evidence suggests that vitamin D is involved in the development of pulmonary arterial hypertension (PAH). The aim of this study was to analyze the electrophysiological and contractile properties of pulmonary arteries (PAs) in vitamin D receptor knockout mice ( Vdr - / - ). PAs were dissected and mounted in a wire myograph. Potassium membrane currents were recorded in freshly isolated PA smooth muscle cells (PASMCs) using the conventional whole-cell configuration of the patch-clamp technique. Potential vitamin D response elements (VDREs) in Kv7 channels coding genes were studied, and their protein expression was analyzed. Vdr - / - mice did not show a pulmonary hypertensive phenotype, as neither right ventricular hypertrophy nor endothelial dysfunction was apparent. However, resistance PA from these mice exhibited increased response to retigabine, a Kv7 activator, compared to controls and heterozygous mice. Furthermore, the current sensitive to XE991, a Kv7 inhibitor, was also higher in PASMCs from knockout mice. A possible VDRE was found in the gene coding for KCNE4, the regulatory subunit of Kv7.4. Accordingly, Vdr - / - mice showed an increased expression of KCNE4 in the lungs, with no changes in Kv7.1 and Kv7.4. These results indicate that the absence of Vdr in mice, as occurred with vitamin D deficient rats, is not sufficient to induce PAH. However, the contribution of Kv7 channel currents to the regulation of PA tone is increased in Vdr -/- mice, resembling animals and humans suffering from PAH. |
