title: Endothelium-Independent Effect of Fisetin on the Agonist-Induced Regulation of Vascular Contractility.
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 A2- 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.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Catholic University of Daegu, Gyeongbuk 38430, Republic of Korea.
authors.forename: Hyun Dong
authors.initials: HD
authors.lastname: Je
authors.affiliation: Department of Pharmacology, College of Pharmacy, Chung Ang University, Seoul 06974, Republic of Korea.
authors.forename: Uy Dong
authors.initials: UD
authors.lastname: Sohn
authors.affiliation: Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 14662, Republic of Korea.
authors.forename: Hyen-Oh
authors.initials: HO
authors.lastname: La
keywords: ERK1/2; Fisetin; Fluoride; MYPT1; Phorbol ester; Rho-kinase