Heaps Cristine L, Robles Juan Carlos, Sarin Vandana, Mattox Mildred L, Parker Janet L
Michael E. DeBakey Institute for Comparative Cardiovascular Science and Biomedical Devices, Texas A&M University, College Station, Texas, USA; Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Microcirculation. 2014 Jul;21(5):388-400. doi: 10.1111/micc.12116.
The aim of this study was to test the hypothesis that exercise training enhances sustained relaxation to persistent endothelium-dependent vasodilator exposure via increased nitric oxide contribution in small coronary arteries of control and ischemic hearts.
Yucatan swine were designated to a control group or a group in which an ameroid constrictor was placed around the proximal LCX. Subsequently, pigs from both groups were assigned to exercise (five days/week; 16 weeks) or SED regimens. Coronary arteries (~100-350 μm) were isolated from control pigs and from both nonoccluded and collateral-dependent regions of chronically-occluded hearts.
In arteries from control pigs, training significantly enhanced relaxation responses to increasing concentrations of bradykinin (10(-10) -10(-7) M) and sustained relaxation to a single bradykinin concentration (30 nM), which were abolished by NOS inhibition. Training also significantly prolonged bradykinin-mediated relaxation in collateral-dependent arteries of occluded pigs, which was associated with more persistent increases in endothelial cellular Ca(2+) levels, and reversed with NOS inhibition. Protein levels for eNOS and p-eNOS-(Ser1179), but not caveolin-1, Hsp90, or Akt, were significantly increased with occlusion, independent of training state.
Exercise training enhances sustained relaxation to endothelium-dependent agonist stimulation in small arteries of control and ischemic hearts by enhanced nitric oxide contribution and endothelial Ca(2+) responses.
本研究旨在验证以下假设：运动训练可通过增加一氧化氮的作用，增强对照心脏和缺血心脏的小冠状动脉对持续内皮依赖性血管舒张剂暴露的持续舒张反应。
将尤卡坦猪分为对照组或在左回旋支近端放置阿梅罗氏缩窄器的组。随后，将两组猪分别分配至运动组（每周五天；16周）或静态组。从对照猪以及慢性闭塞心脏的非闭塞区和侧支依赖区分离出冠状动脉（约100 - 350μm）。
在对照猪的动脉中，训练显著增强了对递增浓度缓激肽（10(-10) - 10(-7)M）的舒张反应以及对单一缓激肽浓度（30 nM）的持续舒张反应，一氧化氮合酶抑制可消除这些反应。训练还显著延长了闭塞猪侧支依赖动脉中缓激肽介导的舒张，这与内皮细胞钙（Ca(2+)）水平更持久的升高相关，且一氧化氮合酶抑制可使其逆转。无论训练状态如何，随着闭塞，内皮型一氧化氮合酶（eNOS）和磷酸化eNOS（Ser1179）的蛋白水平显著升高，但小窝蛋白-1、热休克蛋白90或蛋白激酶B（Akt）的蛋白水平未升高。
运动训练通过增强一氧化氮的作用和内皮钙（Ca(2+)）反应，增强对照心脏和缺血心脏小动脉对内皮依赖性激动剂刺激的持续舒张反应。
