Hodnett Benjamin L, Xiang Lusha, Dearman Jennifer A, Carter Cory B, Hester Robert L
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
Microcirculation. 2008 Aug;15(6):485-94. doi: 10.1080/10739680801942240.
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 K(ATP) channel-mediated vasodilation.
K(ATP) channel function was determined in isolated skeletal muscle arterioles in response to the K(ATP) opener cromakalim (0.1-10 microM) during normal myogenic tone and alpha-adrenergic-mediated tone (0.1 microM phenylephrine). The spinotrapezius muscle was prepared and the vasodilatory responses to muscle stimulation or iloprost (0.028-2.8 microM) were observed before and after the application of the K(ATP) inhibitor, glibenclamide (10 microM). Channel subunit expression was determined by using western blot analyses.
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 a nimals. Channel subunit expression was similar in femoral arteries.
The impaired functional vasodilation in the OZR is associated with altered K(ATP) channel sensitivity.
肥胖状态下运动期间骨骼肌血流量受损。我们检验了以下假设：肥胖 Zucker 大鼠（OZR）骨骼肌小动脉中血管舒张减弱是由于 K(ATP) 通道介导的血管舒张改变所致。
在正常肌源性张力和α-肾上腺素能介导的张力（0.1 μM 去氧肾上腺素）期间，测定分离的骨骼肌小动脉对 K(ATP) 开放剂克罗卡林（0.1 - 10 μM）的 K(ATP) 通道功能。制备斜方肌，在应用 K(ATP) 抑制剂格列本脲（10 μM）前后，观察对肌肉刺激或伊洛前列素（0.028 - 2.8 μM）的血管舒张反应。通过蛋白质印迹分析确定通道亚基表达。
与瘦对照组相比，OZR 中克罗卡林浓度 - 反应曲线发生偏移。与瘦对照组相比，OZR 表现出功能和伊洛前列素诱导的血管舒张受损。格列本脲抑制瘦大鼠的功能和伊洛前列素诱导的舒张，对肥胖动物无影响。股动脉中通道亚基表达相似。
OZR 中功能性血管舒张受损与 K(ATP) 通道敏感性改变有关。
