Comparison of the cardiovascular effects of two 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 (2R,3R,8R,9R-bis-cyclohexano-1,4,7,10,13-pentaazacyclopentadeca ne)] (n = 10) and SC-55417 [Manganese (II) dichloro (trans-2,3-cyclohexano-1,4,7,10,13-pentaazacyclopentadecane) ] (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 microM.kg-1.min-1 SC-55858 or SC-54417 (total doses of 1, 2, 7, and 20 microM.kg-1). SC-55858 and SC-54417 increased heart rate and decreased mean arterial pressure and left ventricular systolic and end-diastolic pressures. SC-55858 decreased preload recruitable stroke work slope and +dP/dtmax and increased the time constant of isovolumic relaxation, consistent with a direct negative inotropic and lusitropic effect. In contrast, SC-54417 did not depress left ventricular systolic and diastolic function. Decreases in mean arterial pressure caused by SC-55858 may be secondary to negative inotropic effects and reduction in cardiac preload. In contrast, SC-54417 does not depress myocardial contractility but also reduces arterial pressure via venodilation.