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• W1506614352 abstract "Chloride (Cl − ) channels expressed in vascular smooth muscle cells (VSMC) are important to control membrane potential equilibrium, intracellular pH, cell volume maintenance, contraction, relaxation and proliferation. The present study was designed to compare the expression, regulation and function of CFTR Cl − channels in aortic VSMC from Cftr +/+ and Cftr − / − mice. Using an iodide efflux assay we demonstrated stimulation of CFTR by VIP, isoproterenol, cAMP agonists and other pharmacological activators in cultured VSMC from Cftr +/+ . On the contrary, in cultured VSMC from Cftr − / − mice these agonists have no effect, showing that CFTR is the dominant Cl − channel involved in the response to cAMP mediators. Angiotensin II and the calcium ionophore A23187 stimulated Ca 2 + ‐dependent Cl − channels in VSMCs from both genotypes. CFTR was activated in myocytes maintained in medium containing either high potassium or 5‐hydroxytryptamine (5‐HT) and was inhibited by CFTR inh ‐172, glibenclamide and diphenylamine‐2,2′‐dicarboxylic acid (DPC). We also examined the mechanical properties of aortas. Arteries with or without endothelium from Cftr −/− mice became significantly more constricted (∼2‐fold) than that of Cftr +/+ mice in response to vasoactive agents. Moreover, in precontracted arteries of Cftr +/+ mice, VIP and CFTR activators induced vasorelaxation that was altered in Cftr −/− mice. Our findings suggest a novel mechanism for regulation of the vascular tone by cAMP‐dependent CFTR chloride channels in VSMC. To our knowledge this study is the first to report the phenotypic consequences of the loss of a Cl − channel on vascular reactivity." @default.
• W1506614352 created "2016-06-24" @default.
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• W1506614352 date "2005-10-01" @default.
• W1506614352 modified "2023-10-18" @default.
• W1506614352 title "Disruption of CFTR chloride channel alters mechanical properties and cAMP‐dependent Cl⁻ transport of mouse aortic smooth muscle cells" @default.
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• W1506614352 doi "https://doi.org/10.1113/jphysiol.2005.085019" @default.
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