Doxorubicin-induced vasomotion and [Ca^2+]i elevation n vascular smooth muscle cells from C57BL/6 mice |
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摘 要: |
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关 键 词: | 血管平滑肌细胞 阿霉素 运动 诱导 小鼠 |
收稿时间: | 2009 May 23 |
Doxorubicin-induced vasomotion and [Ca2+]i elevation in vascular smooth muscle cells from C57BL/6 mice |
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Authors: | BingSHEN Chun-ling YE Kai-he YE Lan ZHUANG Jia-hua JIANG |
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Institution: | [1]Department of Pharmacology, Pharmaceutical College, Ji-nan University, Guangzhou 510632, China [2]Department of Pharmacology, Anhui Medical University, Hefei 230022, China [3]Division of Cardiovascular Research, The Hospital for Sick Children, Toronto, Canada |
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Abstract: | Aim:To explore the action of doxorubicin on vascular smooth muscle cells.Methods:Isometric tension of denuded or intact thoracic aortic vessels was recorded and Ca2+]i in isolated aortic smooth muscle cells was measured by using Fluo-3.Results:Doxorubicin induced phasic and tonic contractions in denuded vessels and increased levels of Ca2+]i in single muscle cells. Treatment with 10 μmol/L ryanodine had no effect on basal tension, but it did abolish doxorubicin-induced phasic contraction. Treatment with 10 mmol/L caffeine induced a transient phasic contraction only, and the effect was not significantly altered by ryanodine, the omission of extracellular Ca2+ or both. Phenylephrine induced rhythmic contraction (RC) in intact vessels. Treatment with 100 μmol/L doxorubicin enhanced RC amplitude, but 1 mmol/L doxorubicin abolished RC, with an increase in maximal tension. Caffeine at 100 μmol/L increased the frequency of the RC only. In the presence of 100 μmol/L caffeine, however, 100 μmol/L doxorubicin abolished the RC and decreased its maximal tension. Treatment with 10 μmol/L ryanodine abolished the RC, with an increase in the maximal tension. In Ca2+-free solution, doxorubicin induced a transient Ca2+]i increase that could be abolished by ryanodine pretreatment in single muscle cells. The doxorubicin-induced increase in Ca2+]i was suppressed by nifedipine and potentiated by ryanodine and charybdotoxin.Conclusion:Doxorubicin not only releases Ca2+ from the sarcoplasmic reticulum but also promotes the entry of extracellular Ca2+ into vascular smooth muscle cells. |
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Keywords: | doxorubicin rhythmic contraction sarcoplasmic reticulum vascular smooth muscle |
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