ATTENUATION OF CHEMOTHERAPY-INDUCED VASCULAR DYSFUNCTION BY EXERCISE TRAINING

Abstract

We have previously shown that exercise training enhances endothelium-dependent vasodilation in a rat mammary tumor model, and that these changes resulted in an attenuation of vasoconstriction caused by the chemotherapeutic agent 5-fluororuacil (5-FU). We hypothesized that this was the result of increased nitric oxide (NO) production by the vasculature. In order to investigate possible mechanisms involved with the exercise-induced attenuation of vascular dysfunction, we determined endothelial nitric oxide synthase (eNOS) protein content in the aorta of N-methyl-N-nitrosourea (MNU)-treated rats following eight weeks of moderate exercise training. Virgin female Sprague Dawley rats were injected with MNU (25 mg/kg, i.p.) at 21 days of age, and at 28 days assigned to either sedentary or exercise groups. The exercise regimen consisted of treadmill running at 20–25 m/min, +15% grade, 30 min/d, 5 d/wk for 8 weeks. Our results show no significant differences in aortic eNOS protein content between sedentary and exercise groups following 2 or 4 weeks of exercise training. However, after 6 weeks of exercise training, significant (p < 0.05) increases in aortic eNOS protein content were observed in exercise trained rats when compared to sedentary animals. Following 8 weeks of exercise training, increases in eNOS protein content were sustained, however differences between sedentary and exercise trained animals were not statistically significant. These data demonstrate that moderate exercise training increases aortic eNOS protein content in a rat mammary tumor model. This suggests that the attenuation of 5-FU-induced vasoconstriction may be due, at least in part, to an increase in aortic eNOS protein content.