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

Troglitazone has direct effects on the hemodynamics of the heart. We investigated the effects of other insulin-sensitizing agents (rosiglitazone, pioglitazone 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 perfused rat hearts. Rosiglitazone significantly decreased heart rate and coronary perfusion pressure, and increased peak isovolumic left ventricular pressure, peak rate of rise of left ventricular pressure and peak rate of fall of left ventricular pressure. The effects of rosiglitazone, however, were milder than those of troglitazone. Neither pioglitazone nor JTT-501 had any effect on the heart. D-alpha-tocopherol, a structural component of troglitazone, did not exert any effect on the heart. The coronary vasorelaxant effect of troglitazone and rosiglitazone was significantly suppressed by indomethacin, but not by N(omega)-nitro-L-arginine methyl ester. In conclusion, only rosiglitazone, as well as troglitazone, exerted positive inotropic, positive lusitropic, negative chronotropic, and coronary vasorelaxant effects on the heart. The coronary vasorelaxant effect of troglitazone and rosiglitazone was mediated by prostaglandin production.