Therapeutic effects of CPU 86017 on acute and chronic congestive cardiac failure mediated by reducing ET‐1?NOS and oxidative stress in rats

CPU 86017, a derivative of berberine, was administered to rats in which acute and chronic heart failure was induced by left coronary artery ligation for 3 h and 8 weeks, respectively. The rats were divided into the following groups: sham operation, coronary artery ligation (CAL), CAL+ CPU 86017 (80?40 and 20 mg/kg, ig) and CAL+ captopril (60 mg/kg, ig). In the acute model, the systolic parameters of LVSP and LV+dp/dtmax as well as the diastolic parameters of LVEDP and LV‐dp/dtmin improved significantly on pretreatment of CPU 86017 (80 mg/kg). Reductions in elevated serum CPK?LDH?MDA?GOT?GPT?infarcted area and blood viscosity were also significant ( P < 0.01). In the chronic model, CPU 86017 (80 mg/kg) preserved the systolic parameters of LVSP and LV+dp/dtmax and the diastolic function of the LVEDP and LV‐dp/dtmin. CPU 86017 completely suppressed elevated plasma ANP and ET‐1, serum and tissue iNOS?NO and MDA, whereas the decreased SOD was improved. CPU 86017 and captopril improved cardiac failure performance and regressed cardiac remodeling in CHF by reducing tissue weight index: lung weight/body weight (BW), right ventricular weight/BW, and left ventricular weight/BW. CPU 86017 exerted beneficial actions in cardiac performance in models of both acute and chronic heart failure, mainly by suppressing ET‐1, iNOS, and oxidative stress in infarcted tissue. Drug Dev Res 63:22–32, 2004.