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Biphasic Effects of Rosiglitazone on Agonist-induced Regulation of Vascular Contractility  

Park, Jin-Gun (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
Je, Hyun-Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
Publication Information
YAKHAK HOEJI / v.51, no.5, 2007 , pp. 301-306 More about this Journal
Abstract
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.
Keywords
KCl; NaF; phorbol 12,13-dibutyrate; Rho-kinase; rosiglitazone; thromboxane $A_2$ mimetic;
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