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  • Title: Underlying mechanisms preserving coronary basal tone and NO-mediated relaxation in obesity: Involvement of β1 subunit-mediated upregulation of BKCa channels.
    Author: Climent B, Sánchez A, Moreno L, Pérez-Vizcaíno F, García-Sacristán A, Rivera L, Prieto D.
    Journal: Atherosclerosis; 2017 Aug; 263():227-236. PubMed ID: 28672269.
    Abstract:
    BACKGROUND AND AIMS: The impact of obesity on vasomotor regulation of coronary arteries and its underlying mechanisms are not completely understood and, in particular, the role of BKCa channels in the NO-mediated coronary vasodilation in obesity remains to be elucidated. METHODS: The effects of selective blockade of BKCa channel was tested on nitric oxide (NO)-mediated vasodilator responses of coronary arteries from lean and obese Zucker rats (LZR and OZR, respectively) by means of simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) by Fura-2 fluorescence and tension in endothelium-denuded coronary arteries mounted in microvascular myographs. BKCa channel subunits expression was measured by Western blot. RESULTS: The selective BKCa channel blocker iberitoxin largely reduced the relaxations and decreases in [Ca2+]i induced by a NO donor in coronary arteries from OZR. Iberitoxin increased to a great extent both basal [Ca2+]i and tone in OZR. The agonist of the voltage-gated L-type calcium channels Bay K8644 induced an increase in [Ca2+]i and tone that was significantly smaller in arteries from OZR, which was restored to control levels in LZR after BKCa channel inhibition. Caffeine- and ryanodine-induced intracellular Ca2+ mobilization and BKCa channel β1 subunit expression were increased in arteries from OZR. CONCLUSIONS: The present study suggests that an enhanced activity of VSM BKCa channels, associated with up-regulation of channel β1 subunit and with a higher intracellular Ca2+ mobilization, contributes to the preserved NO-mediated vasodilatation and basal tone of coronary arteries in obesity.
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