Impaired Vascular KATP Function Attenuates Exercise Capacity in Obese Zucker Rats
Article first published online: 12 OCT 2013
© 2013 John Wiley & Sons Ltd
Volume 20, Issue 7, pages 662–669, October 2013
How to Cite
Impaired vascular KATP function attenuates exercise capacity in obese Zucker rats. Microcirculation 20: 662–669, 2013., , , , , .
- Issue published online: 12 OCT 2013
- Article first published online: 12 OCT 2013
- Accepted manuscript online: 7 MAY 2013 06:19AM EST
- Manuscript Accepted: 2 MAY 2013
- Manuscript Received: 8 JAN 2013
- NIH. Grant Numbers: HL-89581, HL-51971, T32 HL-105324
- NADPH oxidase;
- KATP channels
Obese subjects exhibit decreased exercise capacity (VO2max). We have shown that vascular KATP channel mediates arteriolar dilation to muscle contraction. We hypothesize that exercise capacity is decreased in obesity due to impaired vascular KATP function.
The VO2max was measured in LZR and OZR by treadmill running before and following treatment with the KATP 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 KATP 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.
The 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.
Exercise capacity is dependent on vascular KATP channel function. The reduced exercise capacity in OZR appears to be due in part to superoxide-mediated impairment in vascular KATP function.