Doxorubicin-induced vasomotion and [Ca^2＋]i elevation n vascular smooth muscle cells from C57BL/6 mice  

作　　者：BingSHEN Chun-ling YE Kai-he YE Lan ZHUANG Jia-hua JIANG 

机构地区：[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

出　　处：《Acta Pharmacologica Sinica》2009年第11期1488-1495,共8页中国药理学报（英文版）

基　　金：Acknowledgements This project was supported by the National Natural Science Foundation of China （No 30070873）.

摘　　要：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 [Ca^2＋]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 [Ca^2＋]i in single muscle cells. Treatment with 10 pmol/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 Ca^2＋ or both. Phenylephrine induced rhythmic contraction （RC） in intact vessels. Treatment with 100 pmol/L doxorubicin enhanced RC amplitude, but 1 mmol/L doxorubicin abolished RC, with an increase in maximal tension. Caffeine at 100 pmol/L increased the frequency of the RC only. In the presence of 100 pmol/L caffeine, however, 100 pmol/L doxorubicin abolished the RC and decreased its maximal tension. Treatment with 10 pmol/L ryanodine abolished the RC, with an increase in the maximal tension. In Ca^2＋-free solution, doxorubicin induced a transient [Ca^2＋]i increase that could be abolished by ryanodine pretreatment in single muscle cells. The doxorubicin-induced increase in [Ca^2＋]i was suppressed by nifedipine and potentiated by ryanodine and charybdotoxin. Conclusion： Doxorubicin not only releases Ca^2＋ from the sarcoplasmic reticulum but also promotes the entry of extracellular Ca^2＋ into vascular smooth muscle cells.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 [Ca^2＋]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 [Ca^2＋]i in single muscle cells. Treatment with 10 pmol/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 Ca^2＋ or both. Phenylephrine induced rhythmic contraction （RC） in intact vessels. Treatment with 100 pmol/L doxorubicin enhanced RC amplitude, but 1 mmol/L doxorubicin abolished RC, with an increase in maximal tension. Caffeine at 100 pmol/L increased the frequency of the RC only. In the presence of 100 pmol/L caffeine, however, 100 pmol/L doxorubicin abolished the RC and decreased its maximal tension. Treatment with 10 pmol/L ryanodine abolished the RC, with an increase in the maximal tension. In Ca^2＋-free solution, doxorubicin induced a transient [Ca^2＋]i increase that could be abolished by ryanodine pretreatment in single muscle cells. The doxorubicin-induced increase in [Ca^2＋]i was suppressed by nifedipine and potentiated by ryanodine and charybdotoxin. Conclusion： Doxorubicin not only releases Ca^2＋ from the sarcoplasmic reticulum but also promotes the entry of extracellular Ca^2＋ into vascular smooth muscle cells.

关 键 词：DOXORUBICIN rhythmic contraction sarcoplasmic reticulum vascular smooth muscle 

分 类 号：Q463[生物学—生理学] TQ465[化学工程—制药化工]