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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Olivan-Viguera, Aida | - |
dc.contributor.author | Valero Gracia, Marta Sofía | - |
dc.contributor.author | Pinilla, Estéfano | - |
dc.contributor.author | Amor, Sara | - |
dc.contributor.author | García-Villalón, Ángel Luis | - |
dc.contributor.author | Coleman, Nichole | - |
dc.contributor.author | Laría, Celia | - |
dc.contributor.author | Calvín-Tienza, Víctor | - |
dc.contributor.author | García-Otín, Ángel Luis | - |
dc.contributor.author | Fernández-Fernández, José Manuel | - |
dc.contributor.author | Murillo, Mª Divina | - |
dc.contributor.author | Gálvez, José Antonio | - |
dc.contributor.author | Díaz-De-Villegas, Maŕia Dolores | - |
dc.contributor.author | Badorrey, Ramón | - |
dc.contributor.author | Simonsen, Ulf | - |
dc.contributor.author | Rivera, Luis | - |
dc.contributor.author | Wulff, Heike | - |
dc.contributor.author | Köhler, Ralf | - |
dc.date.accessioned | 2021-02-19T12:40:44Z | - |
dc.date.available | 2021-02-19T12:40:44Z | - |
dc.date.issued | 2019-03-01 | - |
dc.identifier.citation | Oliván-Viguera, A., Valero, M.S., Pinilla, E., Amor, S., García-Villalón, Á.L., Coleman, N., Laría, C., Calvín-Tienza, V., García-Otín, Á.-L., Fernández-Fernández, J.M., Murillo, M.D., Gálvez, J.A., Díaz-De-Villegas, M.D., Badorrey, R., Simonsen, U., Rivera, L., Wulff, H., Köhler, R., 2016. Vascular Reactivity Profile of Novel KCa3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed. Basic & Clinical Pharmacology & Toxicology 119, 184–192.. doi:10.1111/bcpt.12560 | es_ES |
dc.identifier.issn | 1742-7835 | es_ES |
dc.identifier.uri | https://repositorio.usj.es/handle/123456789/486 | - |
dc.description.abstract | Abstract: Opening of intermediate-conductance calcium-activated potassium channels (KCa3.1) produces membrane hyperpolarization in the vascular endothelium. Here, we studied the ability of two new KCa3.1-selective positive-gating modulators, SKA111 and SKA-121, to (1) evoke porcine endothelial cell KCa3.1 membrane hyperpolarization, (2) induce endothelium-dependent and, particularly, endothelium-derived hyperpolarization (EDH)-type relaxation in porcine coronary arteries (PCA) and (3) influence coronary artery tone in isolated rat hearts. In whole-cell patch-clamp experiments on endothelial cells of PCA (PCAEC), KCa currents evoked by bradykinin (BK) were potentiated 7-fold by either SKA-111 or SKA-121 (both at 1 lM) and were blocked by a KCa3.1 blocker, TRAM-34. In membrane potential measurements, SKA-111 and SKA-121 augmented bradykinininduced hyperpolarization. Isometric tension measurements in large- and small-calibre PCA showed that SKA-111 and SKA-121 potentiated endothelium-dependent relaxation with intact NO synthesis and EDH-type relaxation to BK by 2-fold. Potentiation of the BK response was prevented by KCa3.1 inhibition. In Langendorff-perfused rat hearts, SKA-111 potentiated coronary vasodilation elicited by BK. In conclusion, our data show that positive-gating modulation of KCa3.1 channels improves BKinduced membrane hyperpolarization and endothelium-dependent relaxation in small and large PCA as well as in the coronary circulation of rats. Positive-gating modulators of KCa3.1 could be therapeutically useful to improve coronary blood flow and counteract impaired coronary endothelial dysfunction in cardiovascular disease. | es_ES |
dc.format.extent | 9 p. | es_ES |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Blackwell Publishing Ltd | es_ES |
dc.relation | This work was supported by the Deutsche Forschungsgemeinschaft [KO1899/11-1 to RK]; the Danish Heart Foundation (to RK and US), European Community [FP7-PEOPLE Project 321721]; Department of Industry & Innovation, Government of Aragon [GIPASC-B105 to ALGO, RK, AOV]; and the Fondo de Investigaci?n Sanitaria, Instituto de Salud Carlos III [RIC RD12/0042/0014 Red HERACLES, to RK]. This study received Grant from the Government of Arag?n [GA E-102 to JAG, MDD, RB]; Grant of the Spanish Ministry of Economy and Competitiveness plus FEDER Funds [no SAF2012-31631 to LR and SAF2012-31089 to JMFF]; Grants from the National Institute of Neurological Disorders and Stroke [R21NS072585 to HW]; and from the National Heart, Lung & Blood Institute T32 Training Program in Basic and Translational Cardiovascular Science [T32HL086350 to NC]. | es_ES |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | KCa3.1 | es_ES |
dc.title | Vascular Reactivity Profile of Novel KCa3.1-Selective Positive-Gating Modulators in the Coronary Vascular Bed | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.identifier.doi | DOI: 10.1111/bcpt.12560 | es_ES |
dc.rights.accessrights | info:eu-repo/semantics/openAccess | es_ES |
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