Genistein Attenuates Postischemic Depressed Myocardial Function by Increasing Myofilament Ca 2+ Sensitivity in Rat Myocardium 1

Abstract

The present study investigated whether genistein, a broad-spectrum tyrosine kinase inhibitor, could increase the myofilament Ca²⁺ sensitivity and partially reverse postischemic depressed myocardial function. Left ventricular papillary muscles were isolated from adult Wistar rats and loaded with the Ca²⁺ indicator, aequorin. The use of fluorocarbon immersion with hypoxia simulated a model of ischemia. Myofilament responsiveness to Ca²⁺ was evaluated from force-[Ca²⁺], relationship recorded during tetani in papillary muscles. Protein levels of troponin I (Tnl) were measured in postischemic papillary muscles with the Western blot technique. Isometric contraction was depressed during the period of ischemia and remained low after 60 min of reoxygenation without a corresponding significant change of peak [Ca²⁺], in the control group (n = 7). In contrast, the depression of isometric contraction was ameliorated during ischemia in muscle preparations in the presence of genistein (2 μM; n = 8), and postischemic depressed myocardial contractility partially recovered after a 60-min reperfusion. The myofilament Ca²⁺ responsiveness was significantly increased in papillary muscles in the presence of genistein. Protein levels of Tnl were reduced in postischemic papillary muscles, whereas genistein partially restored decreased protein levels of Tnl. Our results reveal that genistein produces an effective attenuation of postischemic depressed myocardial function and improves myofibrillar Ca²⁺ responsiveness in rat myocardium.