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

Je, Hyun Dong; Sohn, Uy Dong; La, Hyen-Oh

doi:10.4062/biomolther.2015.104

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

Biomolecules & therapeutics, v.24 no.1, 2016년, pp.57 - 61

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)

Abstract ▼ AI-Helper

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.

주제어

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문제 정의

However, it has not been reported as to whether this pathway is inhibited during fisetin-induced vascular smooth muscle relaxation in aortic rings precontracted with Rho-kinase activator fluoride or MEK activator phorbol ester. Therefore, the aim of the present study was to investigate the possible roles of Rho-kinase or MEK inhibition on Ca²⁺ desensitization during the fisetin-induced relaxation of isolated rat aortas by using RhoA/Rho-kinase activators fluoride or thromboxane A₂ or a MEK activator phorbol ester excluding endothelial nitric oxide synthesis.

제안 방법

Each relaxing ring was precontracted with 6 mM fluoride. This work was done using quick frozen fisetin (0.1 mM)-treated rat aortas in the absence of endothelium and the levels were compared to those of vehicle-treated rat aortas (Fig. 6). Interestingly, significant decrease in fluoride-induced MYPT1 phosphorylation at Thr855 was found to be led by fisetin (Fig.

대상 데이터

Drugs and chemicals were obtained from the following sources. Sodium fluoride, KCl, acetylcholine, fisetin, U-46619 and phorbol 12,13-dibutyrate were purchased from Sigma (St. Louis, MO, USA). DTT, TCA and acetone were obtained from Fisher Scientific (Hampton, NH, USA).

데이터처리

The student’s unpaired t test or ANOVA was used to determine the statistical significance of the means between two groups using SPSS 12.0 (SPSS Inc., Chicago, Illinois, U.S.A.).

성능/효과

Interestingly, during fluoride-induced contraction, the inhibition of Rho-kinase activity and subsequent MYPT1 phosphorylation induced by fisetin suggest that Rho-kinase inactivation is required for relaxation. In conclusion, in addition to endothelial nitric oxide synthesis in intact muscle which makes synergism, both MEK and Rho-kinase inhibition make a major contribution to the mechanism responsible for fisetin-induced vasorelaxation in the denuded muscle.

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

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

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참고문헌 (26)

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