Yang Yan, Jones Allan W, Thomas Tom R, Rubin Leona J
Department of Biomedical Science, University of Missouri-Columbia, Columbia, MO 65211, USA.
Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1553-63. doi: 10.1152/ajpheart.00151.2007. Epub 2007 May 25.
Potassium channels in vascular smooth muscle (VSM) control vasodilation and are potential regulatory targets. This study evaluated effects of sex differences, exercise training (EX), and high-fat diet (HF) on K(+) currents (I(K)) of coronary VSM cells. Yucatan male and female swine were assigned to either sedentary confinement (SED), 16 wk of EX, 20 wk of HF, or 20 wk of HF with 16 wk of EX (HF-EX). VSM cells of normal-diet SED animals exhibited three components of I(K): 4-aminopyridine-sensitive I(K(KV)), TEA-sensitive I(K(BK)), and 4-aminopyridine + TEA-insensitive I(K). Females exhibited significantly higher basal I(K) than males in the same group. EX increased basal I(K) in males and females. HF reduced I(K) in males and females and nullified effects of EX. Endothelin-1 increased I(K) significantly in males but not in females. In the presence of endothelin-1, 1) I(K(KV)) was similar in SED males and females and EX increased I(K(KV)) to a greater extent in males than in females and 2) I(K(BK)) was greater in SED females than in males and EX increased I(K(BK)) to a greater extent in males, resulting in I(K(BK)) similar to EX females. Importantly, HF nullified effects of EX on I(K(KV)) and I(K(BK)). These data indicate that basal I(K) of SED female swine is inherently greater than that shown in SED males and that males require EX to achieve comparable levels of I(K). Importantly, HF reduced I(K) in males and females and nullified effects of EX, suggesting HF abrogates beneficial effects of EX on coronary smooth muscle.
血管平滑肌(VSM)中的钾通道控制血管舒张,是潜在的调节靶点。本研究评估了性别差异、运动训练(EX)和高脂饮食(HF)对冠状动脉VSM细胞钾电流(I(K))的影响。将尤卡坦半岛的雄性和雌性猪分为久坐圈养组(SED)、16周运动训练组(EX)、20周高脂饮食组(HF)或20周高脂饮食加16周运动训练组(HF-EX)。正常饮食SED动物的VSM细胞表现出I(K)的三个成分:4-氨基吡啶敏感的I(K(KV))、四乙铵敏感的I(K(BK))和4-氨基吡啶+四乙铵不敏感的I(K)。同一组中,雌性的基础I(K)显著高于雄性。EX增加了雄性和雌性的基础I(K)。HF降低了雄性和雌性的I(K),并消除了EX的作用。内皮素-1使雄性的I(K)显著增加,但雌性没有。在内皮素-1存在的情况下,1)SED雄性和雌性的I(K(KV))相似,EX使雄性的I(K(KV))增加的程度大于雌性;2)SED雌性的I(K(BK))大于雄性,EX使雄性的I(K(BK))增加的程度更大,导致I(K(BK))与EX雌性相似。重要的是,HF消除了EX对I(K(KV))和I(K(BK))的作用。这些数据表明,SED雌性猪的基础I(K)天生大于SED雄性猪,并且雄性需要EX才能达到可比的I(K)水平。重要的是,HF降低了雄性和雌性的I(K),并消除了EX的作用,表明HF消除了EX对冠状动脉平滑肌的有益作用。