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Journal Article
Research Support, Non-U.S. Gov't
Underlying mechanisms preserving coronary basal tone and NO-mediated relaxation in obesity: Involvement of β1 subunit-mediated upregulation of BK Ca channels.
Atherosclerosis 2017 August
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.
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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