COMPARISON OF THE CARDIOVASCULAR EFFECTS OF 2 NOVEL SUPEROXIDE-DISMUTASE MIMETICS, SC-55858 AND SC-54417, IN CONSCIOUS DOGS

The hemodynamic actions and left ventricular mechanical effects of two new superoxide dismutase mimetics, SC-55858 [Manganese (II) dichloro cyclohexano-1,4,7,10,13-pentaazacyclopentadecane)] (n = 10) and SC-554 17 [Manganese (II) dichloro cyclohexano-1,4,7,10,13-pentaazacyclopenta decane)] (n = 8), were studied in chronically instrumented dogs in the conscious state and after 30 min equilibration at 0.033, 0.067, 0.233 , and 0.667 mu M . kg(-1). min(-1) SC-55858 or SC-54417 (total doses o f 1, 2, 7, and 20 mu M . kg(-1)). SC-55858 and SC-54417 increased hear t rate and decreased mean arterial pressure and left ventricular systo lic and end-diastolic pressures. SC-55858 decreased preload recruitabl e stroke work slope and +dP/dt(max) and increased the time constant of isovolumic relaxation, consistent with a direct negative inotropic an d lusitropic effect. In contrast, SC-54417 did not depress left ventri cular systolic and diastolic function, Decreases in mean arterial pres sure caused by SC-55858 may be secondary to negative inotropic effects and reduction in cardiac preload. In contrast, SC-54417 does not depr ess myocardial contractility but also reduces arterial pressure via ve nodilation.