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KMID : 0370220070510050301
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Yakhak Hoeji
2007 Volume.51 No. 5 p.301 ~ p.306
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Biphasic Effects of Rosiglitazone on Agonist-induced Regulation of Vascular Contractility
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Park Jin-Gun
Je Hyun-Dong
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Abstract
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Rosiglitazone (Avandia^{(R)}) represents a new class of antidiabetic drugs which are PPAR{gamma} agonists. The present study was undertaken to determine whether the new antidiabetic rosiglitazone influences on the agonist-induced regulation of vascular smooth muscle contraction as an antihypertensive and, if so, to investigate the related mechanism. Endothelium-denuded arterial rings from male Sprague-Dawley rats were used and isometric contractions were recorded using a computerized data acquisition system. Rosiglitazone decreased Rho-kinase activating agonist (NaF or thromboxane A_2 mimetic)-induced contraction but not depolarization- or phorbol ester-induced contraction. Surprisingly, it slightly potentiated the latter contraction possibly opening a voltage-dependent calcium channel by its chemical structure on 50 mM KCI- or 1{mu}M phorbol 12,13-dibutyrate-induced vasoconstriction. In conclusion, this study provides the evidence and possible related mechanism concerning the biphasic effect of an antidiabetic rosiglitazone as a possible antihypertensive on the agonistinduced contraction in rat aortic rings regardless of endothelial function.
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KEYWORD
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KCl, NaF, phorbol 12, 13-dibutyrate, Rho-kinase, rosiglitazone, thromboxane A_2 mimetic
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