Introduction: Little is known regarding the effects of exercise with or without weight loss on the vascular endothelial function in diabetes.
Methods: To address this we exercised db/db and WT mice for 1 hour a day and five days a week with Exercise I (212/day, minimal weight loss) or exercise II (300m/day, 10% weight loss) and compared their aortic endothelial cell function with their sedentary littermates.
Results: Endothelium-dependent relaxation (ACh-induced) was severely impaired in db/db mice aortae compared to WT animals. Exercise significantly improved ACh response independently of weight loss in db/db arteries. Improvement in endothelial function occurred despite the existence of hyperglycemia at the time of sacrifice in exercised db/db mice. Incubation of aortic rings with SOD, a superoxide scavenger, improved vascular responses to ACh in sedentary db/db mice without altering ACh responses in db/db mice trained with exercise-I and exercise-II. The same pattern was found when aortae were incubated with L-Arg and BH4, eNOS substrate and cofactor. In conclusion, in db/db mice increased oxidative stress mediates NO degradation or produces a state of relative deficiency of eNOS substrate and cofactor.
Conclusion: Exercise, independent of weight loss, prevents NO degradation possibly by increasing the antioxidant defense mechanisms and thereby improves endothelial cell function.