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KMID : 0578320090270020191
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Molecules and Cells
2009 Volume.27 No. 2 p.191 ~ p.198
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Inhibitory Effect of Genistein on Agonist-Induced Modulation of Vascular Contractility
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Je Hyun-Dong
Sohn Uy-Dong
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Abstract
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The present study was undertaken to determine whether treatment with genistein, the plant-derived estrogen-like compound influences agonist-induced vascular smooth muscle contraction and, if so, to investigate related mechanisms. The measurement of isometric contrac-tions using a computerized data acquisition system was combined with molecular experiments. Genistein com-pletely inhibited KCl-, phorbol ester-, phenylephrine-, fluoride- and thromboxane A2-induced contractions. An inactive analogue, daidzein, completely inhibited only fluoride-induced contraction regardless of endothelial function, suggesting some difference between the mechanisms of RhoA/Rho-kinase activators such as fluoride and thromboxane A2. Furthermore, genistein and daidzein each significantly decreased phosphorylation of MYPT1 at Thr855 had been induced by a thromboxane A2 mimetic. Interestingly, iberiotoxin, a blocker of large-conductance calcium-activated potassium channels, did not inhibit the relaxation response to genistein or daidzein in denuded aortic rings precontracted with fluoride. In conclusion, genistein or daidzein elicit similar relaxing responses in fluoride-induced contractions, regardless of tyrosine kinase inhibition or endothelial function, and the relaxation caused by genistein or daidzein was not antagonized by large conductance KCa-channel inhibitors in the denuded muscle. This suggests that the RhoA/Rho-kinase pathway rather than K+-channels are involved in the genistein-induced vasodilation. In addition, based on molecular and physiological results, only one vasoconstrictor fluoride seems to be a full RhoA/Rho-kinase activator; the others are partial activators.
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KEYWORD
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Ca2+-activated K+ channels, fluoride, MYPT1, Rho-kinase, thromboxane A2 mimetic, tyrosine kinase, vasodilation
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