Abstract
Previous studies showed that berberine, an alkaloid from Coptis Chinensis Franch, might exert a positive inotropic effect on the heart. However, the underlying mechanisms were unclear. Here, we reported that berberine at 10–20 µM increased the left ventricular (LV) developed pressure and the maximal rate of the pressure rising, and it increased the maximal rate of the pressure descending at 20 µM in Langendorff-perfused isolated rat hearts. These effects diminished with the concentration of berberine increasing to 50 µM. In the concentration range of 50–300 µM, berberine increased the isometric tension of isolated left ventricular muscle (LVM) strips with or without electrical stimulations, and it (30–300 µM) also increased the intracellular Ca2+ level in the isolated LV myocytes. The removal of extracellular Ca2+ hindered the berberine-induced increases in the tension of LVM strips and the intracellular Ca2+ level of LV myocytes. These suggested that berberine might exert its positive inotropic effects via enhancing Ca2+ influx. The blockade of L-type Ca2+ channels (LTCCs) with nifedipine significantly attenuated 300 μM berberine-induced tension increase in LVM strips but not the increase in the intracellular Ca2+ level. Berberine (300 μM) further increased the LVM tension following the treatment with the LTCC opener FPL-64716 (10 μM), indicating an LTCC-independent effect of berberine. Lowering extracellular Na+ attenuated the berberine-induced increases in both the tension of LVM strips and the intracellular Ca2+ level of LV myocytes. In conclusion, berberine might exert a positive inotropic effect on the isolated rat heart by enhancing the Ca2+ influx in LV myocytes; these were extracellular Na+-dependent.
Highlights
Berberine is an alkaloid present in numerous plants, including Coptis Chinensis Franch, and has been used for the treatment of gastrointestinal infections and diarrhea in Asian countries, in China
The left ventricular pressure (LVP) wasW continuously recorded for at least 30 min at each concentration of berberine until it reached a stable level, which was defined as the variation of LVP amplitude was less than 10% within 5 min
Following the perfusion of berberine (10 μM), left ventricular developed pressure (LVDP), +dp/dtmax, and |−dp/dt|max increased to 129.0 ± 11.4%, 112.3 ± 8.0%, and 110.0 ± 9.3% of the basal levels, respectively; they decreased with time to 84.0 ± 5.8%, 83.1 ± 4.8%, and 81.5 ± 5.8% of the basal levels in the absence of berberine, respectively
Summary
Berberine is an alkaloid present in numerous plants, including Coptis Chinensis Franch, and has been used for the treatment of gastrointestinal infections and diarrhea in Asian countries, in China. Berberine increased the developed force in the isolated left atrium of guinea pigs by enhancing both the force-velocity relationship and the duration of the active state (Shaffer, 1985). The contractile capability of the left ventricle is critical for heart function. As the left ventricle contracts, the pressure rises to a level that is high enough to pump blood into systemic circulation through the aorta (Bombardini, 2005). There is no study about the berberine effect on the LV contractility, which is vital for the pumping capability of the heart, and the underlying mechanisms by which berberine affects the left ventricle remains to be determined
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