Doxorubicin-induced vasomotion and [Ca(2+)](i) elevation in vascular smooth muscle cells from C57BL/6 mice.
OBJECTIVE
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 micromol/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 micromol/L doxorubicin enhanced RC amplitude, but 1 mmol/L doxorubicin abolished RC, with an increase in maximal tension. Caffeine at 100 micromol/L increased the frequency of the RC only. In the presence of 100 micromol/L caffeine, however, 100 micromol/L doxorubicin abolished the RC and decreased its maximal tension. Treatment with 10 micromol/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.


CONCLUSIONS
Doxorubicin not only releases Ca(2+) from the sarcoplasmic reticulum but also promotes the entry of extracellular Ca(2+) into vascular smooth muscle cells.
Shen
Bing
B
Department of Pharmacology, Pharmaceutical College, Ji-nan University, Guangzhou, China.
Ye
Chun-ling
CL
Ye
Kai-he
KH
Zhuang
Lan
L
Jiang
Jia-hua
JH
D000814:Aniline Compounds; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D005456:Fluorescent Dyes; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014966:Xanthenes
D000814:Aniline Compounds; D000903:Antibiotics, Antineoplastic; D005456:Fluorescent Dyes; D014966:Xanthenes; C059715:Fluo-3; D004317:Doxorubicin; D002118:Calcium