Exercise Training Attenuates Radiation‐Induced Impairments in Endothelium‐Dependent Vasodilation of Coronary Arterioles in Rats

Abstract

BackgroundRadiation is an important and effective anti‐cancer therapy, but is associated with many side effects. Radiation exposure may cause damage to the heart and coronary vasculature. Exercise training is currently being investigated in cancer research as a treatment or adjuvant to anti‐cancer therapies, and has been shown to mitigate deleterious changes in coronary vascular function, such as with aging. We hypothesized that impairments in endothelium‐dependent vasodilation of coronary resistance arterioles that occur in response to radiation exposure would be mitigated with exercise training.Methods12 male Fischer 344 rats (3‐4 months old) were randomly assigned to one of four groups: control (CON; n=3), exercise (EX; n=3), control radiated (RAD; n=3), or exercise radiated (EX RAD; n=3). After increasing intensity over the first 3 weeks, EX and EX RAD animals ran on a motorized treadmill 5 days/week for 60 minutes/day, at an intensity of 15 m/min and 15° incline for the remainder of 12 weeks of training. After the conclusion of exercise training, all groups of animals were subjected 2 Gy whole body radiation by X‐Rad 350 x‐ray irradiator and euthanized within 8 hours. Hearts were harvested and left anterior descending (LAD) arteriole sections were isolated and fixed on glass pipets. Vessels were pressurized at 60 cm H2O. Once a minimum of 20% tone was developed, vessels were exposed to cumulative doses of bradykinin (10‐13‐10‐7 M), an endothelium‐dependent vasodilator, and vessel diameter was recorded at each dose.ResultsNo differences were detected for CON vs. EX or CON vs. EX RAD. Vasodilation for RAD was significantly reduced vs. CON (p = 0.007). EX RAD was significantly increased vs. RAD (p = 0.025).ConclusionsThere were no differences between CON and EX; however, vasodilation was impaired for radiated animals, suggesting even one dose of 2 Gy radiation can cause significant impairment in endothelium‐dependent vasodilation of coronary arterioles. Exercise training attenuated this impairment and restored endothelium‐dependent vasodilation to levels not different from control animals. These findings are significant, given that exercise training may be used as a simple and safe method to preserve coronary arteriole function in patients receiving radiation therapy.