INOTROPIC, CHRONOTROPIC, AND RADIOLIGAND BINDING CHARACTERISTICS OF LEUKOTRIENE B-4 IN CARDIAC MYOCYTE, PAPILLARY-MUSCLE, AND MEMBRANE PREPARATIONS

Cardioprotective effects of dietary fish oil consumption have been att ributed to the substitution of eicosapentaenoic acid (EPA) for arachid onic acid (AA) in cellular membranes. This substitution blocks the for mation of leukotriene B-4 (LTB(4)) which is elaborated locally in the area of ischemic myocardium. We studied the in vitro inotropic, chrono tropic, and radioligand binding characteristics of LTB(4) to gain pote ntially important insights into the mechanisms involved in the cardiop rotective effect of EPA. LTB(4) was a concentration-dependent and reve rsible negative inotrope in isolated papillary muscle preparations. LT B(4) significantly blocked the positive inotropic effect of Bay K 8644 (BK) (calcium channel regulator) on papillary muscles and the positiv e chronotropic effect of BK on spontaneously beating neonatal cardiac myocytes. LTB(4) had no direct effect on [H-3]PN200-110 binding to car diac sarcolemmal L-type calcium channels or [H-3]ryanodine binding to cardiac SR calcium release channels. These studies support a potential ly important indirect effect of LTB(4) on myocardial E-C coupling.