Griffin K L, Woodman C R, Price E M, Laughlin M H, Parker J L
Dalton Cardiovascular Research Center, University of Missouri, Columbia, USA.
Circulation. 2001 Sep 18;104(12):1393-8. doi: 10.1161/hc3601.094274.
Endothelium-dependent modulation of coronary tone is impaired in the collateral-dependent coronary microcirculation. We used a porcine model of chronic coronary occlusion and collateral development to evaluate the hypothesis that exercise training enhances endothelium-mediated relaxation and increases endothelial nitric oxide synthase (ecNOS) mRNA levels of collateral-dependent microvasculature.
Adult female miniature swine were subjected to chronic, progressive ameroid occlusion of the proximal left circumflex coronary artery (LCx); after 2 months, animals were randomly exposed to 16-week exercise-training (EX group; treadmill running) or sedentary (SED group; cage confinement) protocols. After completion of EX or SED programs, coronary arterioles ( approximately 100 microm in diameter) were isolated from collateral-dependent LCx (distal to occlusion) and nonoccluded left anterior descending coronary artery (LAD) regions of each heart. Arterioles were studied by in vitro videomicroscopy or frozen for ecNOS mRNA analysis (RT-PCR techniques). Relaxation to the endothelium-dependent vasodilator bradykinin was decreased (P<0.05) in arterioles isolated from collateral-dependent LCx versus nonoccluded LAD regions of SED animals. Bradykinin-mediated relaxation, however, was not different in LCx versus LAD arterioles isolated from EX animals. Nitroprusside-induced relaxation was unaffected by either chronic occlusion or exercise. Importantly, ecNOS mRNA expression was significantly decreased in arterioles isolated from LCx versus LAD regions of SED animals. After training, ecNOS mRNA expression was not different between LAD and LCx arterioles.
These data indicate that exercise training enhances bradykinin-mediated relaxation of collateral-dependent LCx arterioles isolated after chronic coronary occlusion, most likely because of effects on ecNOS mRNA expression and increased production of NO.
在依赖侧支循环的冠状动脉微循环中，内皮依赖性冠状动脉张力调节受损。我们使用慢性冠状动脉闭塞和侧支循环发育的猪模型来评估运动训练增强内皮介导的舒张功能并增加依赖侧支循环的微血管内皮型一氧化氮合酶（ecNOS）mRNA水平这一假设。
成年雌性小型猪接受左回旋支冠状动脉（LCx）近端的慢性、渐进性阿梅氏环闭塞；2个月后，动物被随机分为16周运动训练组（EX组；跑步机跑步）或久坐组（SED组；笼养）。在完成EX或SED方案后，从每只心脏的依赖侧支循环的LCx（闭塞远端）和未闭塞的左前降支冠状动脉（LAD）区域分离出冠状动脉小动脉（直径约100微米）。通过体外视频显微镜研究小动脉，或冷冻用于ecNOS mRNA分析（RT-PCR技术）。与SED动物未闭塞的LAD区域相比，从依赖侧支循环的LCx分离出的小动脉对内皮依赖性血管舒张剂缓激肽的舒张反应降低（P<0.05）。然而，从EX动物分离出的LCx与LAD小动脉中，缓激肽介导的舒张没有差异。硝普钠诱导的舒张不受慢性闭塞或运动的影响。重要的是，与SED动物的LAD区域相比，从LCx分离出的小动脉中ecNOS mRNA表达显著降低。训练后，LAD和LCx小动脉之间的ecNOS mRNA表达没有差异。
这些数据表明，运动训练增强了慢性冠状动脉闭塞后分离出的依赖侧支循环的LCx小动脉对缓激肽介导的舒张作用，最可能是由于对ecNOS mRNA表达的影响和一氧化氮生成增加。
