Impaired Vascular KATP Function Attenuates Exercise Capacity in Obese Zucker Rats

ObjectiveObese subjects exhibit decreased exercise capacity (VO2max). We have shown that vascular K-ATP channel mediates arteriolar dilation to muscle contraction. We hypothesize that exercise capacity is decreased in obesity due to impaired vascular K-ATP function. MethodsThe VO2max was measured in LZR and OZR by treadmill running before and following treatment with the K-ATP blocker glibenclamide i.p. One week later, the spinotrapezius muscle was prepared for in vivo microscopy. Arcade arteriolar diameters were measured following muscle contraction or application of the K-ATP opener cromakalim before and after glibenclamide application. In additional animals, LZR and OZR were treated with apocynin for five weeks. VO2max and arteriolar dilation experiments were repeated. ResultsThe OZR exhibited decreased VO2max, functional and cromakalim-induced vasodilation as compared with LZR. Glibenclamide had no effect on VO2max and functional vasodilation in OZR, but significantly inhibited responses in LZR. Vascular superoxide levels and NADPH oxidase activity were increased in OZR, but reduced in apocynin-treated OZR. Apocynin increased the VO2max, functional and cromakalim-induced vasodilation in OZR with no effect in LZR. ConclusionsExercise capacity is dependent on vascular K-ATP channel function. The reduced exercise capacity in OZR appears to be due in part to superoxide-mediated impairment in vascular K-ATP function.