Fogarty Jennifer A, Muller-Delp Judy M, Delp Michael D, Mattox Mildred L, Laughlin M Harold, Parker Janet L
Cardiovascular Research Institute and Department of Medical Physiology, Texas A&M University System Health Science Center, College Station, Tex 77843-1114, USA.
Circulation. 2004 Feb 10;109(5):664-70. doi: 10.1161/01.CIR.0000112580.31594.F9.
Chronic coronary occlusion (CCO) impairs endothelial function of distal collateral-dependent microvasculature; however, long-term exercise training (EX) seems to improve endothelial dysfunction. We hypothesized that EX enhances vasodilation responses to vascular endothelial growth factor (VEGF165), mediated via nitric oxide (NO), in arterioles exposed to CCO.
The proximal left circumflex coronary artery (LCx) of female Yucatan miniswine was surgically instrumented with an ameroid occluder to induce CCO; 8 weeks after surgery, animals were randomized into 14-week sedentary (SED) or EX (treadmill; 5 d/wk) protocols. Coronary arterioles ( approximately 100 microm in diameter) were isolated from collateral-dependent (LCx) and nonoccluded (left anterior descending; LAD) perfused myocardium of SED and EX animals. Vasodilation was assessed by videomicroscopy and MacLab data acquisition. Responses to VEGF165 were unaffected by EX in nonoccluded LAD arterioles; in contrast, EX markedly enhanced VEGF165-induced vasodilation of collateral-dependent LCx arterioles (P<0.05; EX versus SED). Furthermore, VEGF165-induced vasodilation of EX LCx arterioles exceeded that of EX or SED LAD arterioles (P<0.05). Enhanced vasodilation of EX LCx arterioles was abolished by inhibition of NO synthase and tyrosine kinase activity. Combined inhibition of NO synthase and cyclooxygenase decreased VEGF165-induced vasodilation of all vessels.
EX enhances VEGF165-induced vasodilation in arterioles distal to CCO; EX effects seem to be mediated through increases in NO.
慢性冠状动脉闭塞（CCO）会损害远端侧支循环依赖的微血管的内皮功能；然而，长期运动训练（EX）似乎能改善内皮功能障碍。我们假设，EX可增强暴露于CCO的小动脉对血管内皮生长因子（VEGF165）的血管舒张反应，该反应由一氧化氮（NO）介导。
对雌性尤卡坦小型猪的左旋冠状动脉（LCx）近端进行手术，植入阿梅罗氏闭塞器以诱导CCO；术后8周，将动物随机分为14周久坐不动（SED）组或EX组（跑步机训练；每周5天）。从SED组和EX组动物的侧支循环依赖（LCx）和非闭塞（左前降支；LAD）灌注心肌中分离出冠状动脉小动脉（直径约100微米）。通过视频显微镜和MacLab数据采集系统评估血管舒张情况。在非闭塞的LAD小动脉中，EX对VEGF165的反应无影响；相反，EX显著增强了侧支循环依赖的LCx小动脉对VEGF165诱导的血管舒张（P<0.05；EX组与SED组相比）。此外，EX组LCx小动脉对VEGF165诱导的血管舒张超过了EX组或SED组的LAD小动脉（P<0.05）。抑制NO合酶和酪氨酸激酶活性可消除EX组LCx小动脉增强的血管舒张。联合抑制NO合酶和环氧化酶可降低VEGF165诱导的所有血管的血管舒张。
EX可增强CCO远端小动脉对VEGF165诱导的血管舒张；EX的作用似乎是通过增加NO来介导的。
