Acute hemodynamic effects of insulin-sensitizing agents in isolated perfused rat hearts

Troglitazone has direct effects on the hemodynamics of the heart. We invest igated the effects of other insulin-sensitizing agents (rosiglitazone, piog litazone and JTT-501 (4-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]- 3,5-isoxazolidinedione)) on the hemodynamics of the heart using isolated pe rfused rat hearts. Rosiglitazone significantly decreased heart rate and cor onary perfusion pressure, and increased peak isovolumic left ventricular pr essure, peak rate of rise of left ventricular pressure and peak rate of fal l of left ventricular pressure. The effects of rosiglitazone, however, were milder than those of troglitazone. Neither pioglitazone nor JTT-501 had an y effect on the heart. D-alpha-tocopherol, a structural component of trogli tazone, did not exert any effect on the heart. The coronary vasorelaxant ef fect of troglitazone and rosiglitazone was significantly suppressed by indo methacin, but not by N-omega-nitro-L-arginine methyl ester. In conclusion, only rosiglitazone, as well as troglitazone, exerted positive inotropic, po sitive lusitropic, negative chronotropic, and coronary vasorelaxant effects on the heart. The coronary vasorelaxant effect of troglitazone and rosigli tazone was mediated by prostaglandin production. (C) 2000 Elsevier Science B.V. All rights reserved.