Abstract
Objective: Skeletal muscle blood flow during exercise is impaired in obesity. We tested the hypothesis that the attenuated vasodilation in skeletal muscle arterioles of obese Zucker rats (OZR) is due to altered KATP channel-mediated vasodilation.
Materials and Methods: KATP channel function was determined in isolated skeletal muscle arterioles in response to the KATP opener cromakalim (0.1–10 μ M) during normal myogenic tone and α -adrenergic-mediated tone (0.1 μ M phenylephrine). The spinotrapezius muscle was prepared and the vasodilatory responses to muscle stimulation or iloprost (0.028–2.8 μ M) were observed before and after the application of the KATP inhibitor, glibenclamide (10 μ M). Channel subunit expression was determined by using western blot analyses.
Results: Cromakalim concentration-response curves were shifted in OZR as compared to lean controls. OZR exhibited impaired functional and iloprost-induced vasodilation as compared to the lean controls. Glibenclamide inhibited the functional and iloprost-induced dilation in the lean rats with no effects in the obese animals. Channel subunit expression was similar in femoral arteries.
Conclusion:The impaired functional vasodilation in the OZR is associated with altered KATP channel sensitivity.
ACKNOWLEDGMENTS
BL Hodnett and LX contributed equally to this article and both should be considered as first authors. This work was supported by an AHA BGIA (LX), AHA Predoctoral Fellowship (BH), NIH HL51971, and a UMC Intramural Grant.