Training enhances vascular relaxation after chemotherapy-induced vasoconstriction

Purpose: Although evidence is accumulating that suggests regular moderate physical activity improves physiological and psychological well-being of cancer patients undergoing chemotherapy, the mechanisms involved remain unclear. Therefore, the purpose of this study was to determine if exercise training improves endothelium-dependent vasodilation after exposure to the chemotherapeutic agent 5-fluorouracil (5-FU). Methods: Rats were injected with N-methyl-N-nitrosourea (MNU) and assigned to either exercise (EX; treadmill running, 20-25 m.min(-1), 15% grade, 30 min.d(-1), 5 d.wk(-1) for 8 wk) or sedentary (SED) groups. After the exercise training period, aortic rings were obtained and used to assess contractile and relaxation characteristics. In addition, endothelial nitric oxide synthase (eNOS) protein content and eNOS enzyme activity was determined. Results: Exercise training resulted in increased maximal endothelium-dependent vasorelaxation to acetylcholine (ACh, 1 X 10(-5) M) (SED, 56 +/- 3%; exercise, 71 +/- 5%; P < 0.05) after norepinephrine-induced (1 X 10(-7) M) vasoconstriction. Exposure of aortic rings from each group to increasing concentrations of 5-FU (7 X 10(-5)-7 X 10(-3) M) resulted in vasoconstriction. Rings obtained from exercise-trained animals demonstrated enhanced vasorelaxation to ACh (1 X 10(-5) M) after 5-FU-induced vasoconstriction compared with rings obtained from SED animals (P < 0.05). In addition, exercise training enhanced eNOS protein content and eNOS activity. Conclusion: Exercise training enhances endothelium-dependent vasorelaxation after 5-FU-induced vasoconstriction, and this may be due, at least in part, to an increase in aortic eNOS protein content and activity. Such exercise-induced adaptations may help alleviate chemotherapy-related fatigue observed in cancer patients.