Cilostazol induces vasodilation through the activation of Ca(2+)-activated K(+) channels in aortic smooth muscle

Vascular Pharmacology
Hongliang LiWon Sun Park

Abstract

We investigated the vasorelaxant effect of cilostazol and related signaling pathways in phenylephrine (Phe)-induced pre-contracted aortic rings. Cilostazol induced vasorelaxation in a concentration-dependent manner when aortic rings were pre-contracted with Phe. Application of the voltage-dependent K(+) (Kv) channel inhibitor 4-AP, the ATP-sensitive K(+) (K(ATP)) channel inhibitor glibenclamide, and the inwardly rectifying K(+) (Kir) channel inhibitor Ba(2+) did not alter the vasorelaxant effect of cilostazol; however, pre- and post-treatment with the big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel inhibitor paxilline inhibited the vasorelaxant effect of cilostazol. This vasorelaxant effect of cilostazol was reduced in the presence of an adenylyl cyclase or a protein kinase A (PKA) inhibitor, but not a protein kinase G inhibitor. Inside-out single channel recordings revealed that cilostazol induced the activation of BK(Ca) channel activity. The vasorelaxant effect of cilostazol was not affected by removal of the endothelium. In addition, application of a nitric oxide synthase inhibitor and a small-conductance Ca(2+)-activated K(+) (SK(Ca)) channel inhibitor did not affect cilostazol-induced vasorelaxation. We conclude th...Continue Reading

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Citations

Sep 21, 2015·BMC Research Notes·Andrea Carla CelottoPaulo Roberto Barbosa Evora
Apr 20, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yean Chun LohMun Fei Yam
May 18, 2017·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Yasushi NagaoTakehiko Iijima
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Nov 23, 2018·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Yean Chun LohMun Fei Yam
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Aug 3, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Helmy MoawadMohammed A Alkhawlani
Feb 19, 2020·Pharmacology & Therapeutics·Boris ManouryRodolphe Fischmeister

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