Original Article

Doxorubicin-induced vasomotion and [Ca2+]i elevation in vascular smooth muscle cells from C57BL/6 mice

Authors: Bing Shen, Chun-ling Ye, Kai-he Ye, Lan Zhuang, Jia-hua Jiang
DOI: 10.1038/aps.2009.145

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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