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Updated: Aug 8, 2026
Two-photon Imaging of Intracellular Ca2+ Handling and Nitric Oxide Production in Endothelial and Smooth Muscle Cells of an Isolated Rat Aorta
Published on: June 10, 2015
Effect of low-dose doxorubicin on calcium content and norepinephrine response in rat aorta
1Biology Department, University of Central Arkansas, Conway 72032.
Abstract:
Doxorubicin (DXR) is a common antineoplastic agent whose clinical utility is limited by development of a dose-related cardiomyopathy. Recent studies demonstrating DXR toxicity in skeletal muscle suggest that this compound may in fact be a general depressant of muscle function. Although previous studies have reported possible indirect actions of DXR on blood vessels, we have investigated the direct effects of this agent on vascular smooth muscle. Chronic, low-dose treatment of rats with intraperitoneal DXR (12 mg/kg total dose over 4 weeks) had no significant effect on body or heart weight, left ventricular water or calcium content, or aortic water or calcium content. Contractile responses to norepinephrine of thoracic aortic strips taken from DXR-treated rats were attenuated by this treatment, and sensitivity (EC50) of these strips to norepinephrine was significantly reduced compared to controls. These results suggest that DXR may have physiological effects on vascular smooth muscle function at doses which produce no signs of toxicity in cardiac muscle.
Insights
Doxorubicin (DXR) affects vascular smooth muscle function even at low doses. This study found DXR impairs blood vessel contractility without causing cardiac damage, suggesting broader muscle toxicity.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Muscle Biology
Background:
- Doxorubicin (DXR) is an effective antineoplastic agent.
- Its clinical use is limited by dose-related cardiomyopathy.
- Emerging evidence suggests DXR may also affect skeletal muscle.
Purpose of the Study:
- To investigate the direct effects of Doxorubicin on vascular smooth muscle function.
- To determine if DXR impacts vascular contractility at non-cardiotoxic doses.
Main Methods:
- Rats were treated with chronic, low-dose intraperitoneal Doxorubicin over 4 weeks.
- Thoracic aortic strips were isolated and tested for contractile responses to norepinephrine.
- Measurements included body/heart weight, left ventricular and aortic water/calcium content.
Main Results:
- Low-dose Doxorubicin treatment did not significantly alter body weight, heart weight, or cardiac/aortic water and calcium content.
- Contractile responses of aortic smooth muscle to norepinephrine were significantly attenuated in DXR-treated rats.
- Sensitivity (EC50) to norepinephrine was significantly reduced in aortic strips from DXR-treated rats.
Conclusions:
- Doxorubicin exerts direct physiological effects on vascular smooth muscle function.
- These vascular effects occur at doses that do not induce detectable cardiac toxicity.
- DXR may act as a general depressant of muscle function, impacting both cardiac and vascular smooth muscle.
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