Berberine Mediated Positive Inotropic Effects on Rat Hearts via a Ca2+-Dependent Mechanism
| Autor: | Jie Gao, Wang Yaqian, Junli Zhao, Yang Jing, Wenkuan Xin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Inotrope heart Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Berberine Nifedipine berberine Extracellular medicine Myocyte Pharmacology (medical) positive inotropic effect biology Alkaloid lcsh:RM1-950 Coptis chinensis Na+ biology.organism_classification Ca2+ 030104 developmental biology lcsh:Therapeutics. Pharmacology chemistry 030220 oncology & carcinogenesis Intracellular medicine.drug |
| Zdroj: | Frontiers in Pharmacology, Vol 11 (2020) |
| ISSN: | 1663-9812 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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