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http://dx.doi.org/10.4062/biomolther.2015.104

Endothelium-Independent Effect of Fisetin on the Agonist-Induced Regulation of Vascular Contractility  

Je, Hyun Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung Ang University)
La, Hyen-Oh (Department of Pharmacology, College of Medicine, The Catholic University of Korea)
Publication Information
Biomolecules & Therapeutics / v.24, no.1, 2016 , pp. 57-61 More about this Journal
Abstract
Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane $A_2$- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.
Keywords
ERK1/2; Fisetin; Fluoride; MYPT1; Phorbol ester; Rho-kinase;
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