Inotropic and chronotropic activity of berberine on isolated guinea pig atria

The cardiac effects of berberine were studied in isolated right and left atrial preparations from guinea pigs. In spontaneously beating right atria, berberine (1 X 10(-5) -3 X 10(-4) M) caused bradycardia, which was not prevented by atropine (1 X 10(-7) M). Over the same concentration range, berberine increased developed force (dF) in left atria electrically driven at 1.5 Hz. This occurred in both untreated and reserpine-treated tissues as well as in the presence of 5 X 10(-7) M propranolol and 1 X 10(-5) M phentolamine. At a stimulation frequency of 1.5 Hz, left atrial responses to each concentration of berberine reached steady state in approximately 10 min. Concentrations of berberine greater than 3 X 10(-4) M depressed dF and increased resting tone until eventually the left atria failed to contract. Analysis of the effects of berberine on the contractile waveform of left atria showed a concentration-dependent increase in maximal positive dF/dt, maximal negative dF/dt, time to peak tension, and relaxation time. When maximal negative dF/dt was normalized for changes in dF (-dF/dt/dF), berberine showed inhibition of the relaxation process. Berberine had only slight effects on post-rest potentiation and paired pulse stimulation, but enhanced the response of left atria to increases in stimulation frequency. From these results, it appears that berberine has a unique profile of action in isolated guinea pig atrial tissue, showing both positive inotropic and negative chronotropic activity. Berberine produces its positive inotropic effect by enhancing both the force-velocity relationship and the duration of the active state.(ABSTRACT TRUNCATED AT 250 WORDS)