(602.12) Exercise Training Attenuates Radiation-Induced Impairments in Endothelium-Dependent Vasodilation of Coronary Arterioles in Rats

Poster Board Number: E443

Olivia Kunkel (Kansas State University), Dryden Baumfalk (Kansas State University), Andrew Horn (Kansas State University), Brad Behnke (Kansas State University, Johnson Cancer Research Center)

Background:  Radiation 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.

Methods:  12 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.

Results:  No 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).

Conclusions:  There 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.