Exercise training restores adenosine-induced relaxation in coronary arteries distal to chronic occlusion

Exercise training restores adenosine-induced relaxation in coronary arteries distal to chronic occlusion
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DOI:
10.1152/ajpheart.2000.278.6.h1984
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发表时间:
2000-06-01
影响因子:
4.8
通讯作者:
Parker, JL
Parker, JL
中科院分区:
医学2区
文献类型:
--
作者:
Heaps, CL;Sturek, M;Parker, JL

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我们以前曾报道过,犬的侧支依赖性冠状动脉表现出受损的松弛腺苷,但不是硝普钠。相反,运动训练增强了正常猪冠状动脉的腺苷敏感性。这些结果刺激了慢性冠状动脉闭塞和运动训练对cAMP与cGMP介导的舒张产生不同影响的假设。为了验证这一假设,Ameroid封堵器手术放置在近端左回旋冠状动脉(LCx)的雌性尤卡坦小型猪8周前开始久坐或运动训练(跑步机运行,16周)协议。从安静但不运动训练的猪中分离的侧支依赖性LCx与未闭塞的左前降支(LAD)动脉环相比,cAMP依赖性血管扩张剂腺苷(10(-7)至10(-3)M)和异丙肾上腺素(3 × 10(-8)至3 × 10(-5)M)的舒张功能受损。此外,腺苷介导的减少同时紧张和肌浆游离钙受损LCx与LAD动脉从久坐不动,但不运动训练的猪。相反,对cAMP依赖性血管扩张剂forskolin(10(-9)至10(-5)M)和cGMP依赖性血管扩张剂硝普钠(10(-9)至10(-4)M)的舒张反应在久坐或运动训练动物的LCx和LAD动脉中没有差异。这些数据表明,慢性闭塞损害受体依赖性,cAMP介导的舒张;受体非依赖性cAMP和cGMP介导的舒张未受损。重要的是,运动训练恢复cAMP介导的侧支依赖性冠状动脉舒张。
We previously reported that canine collateral-dependent coronary arteries exhibit impaired relaxation to adenosine but not sodium nitroprusside. In contrast, exercise training enhances adenosine sensitivity of normal porcine coronary arteries. These results stimulated the hypothesis that chronic coronary occlusion and exercise training produce differential effects on cAMP-versus cGMP-mediated relaxation. To test this hypothesis, Ameroid occluders were surgically placed around the proximal left circumflex coronary artery (LCx) of female Yucatan miniature swine 8 wk before initiating sedentary or exercise training (treadmill run, 16 wk) protocols. Relaxation to the cAMP-dependent vasodilators adenosine (10(-7) to 10(-3) M) and isoproterenol (3 x 10(-8) to 3 x 10(-5) M) were impaired in collateral-dependent LCx versus nonoccluded left anterior descending (LAD) arterial rings isolated from sedentary but not exercise-trained pigs. Furthermore, adenosine-mediated reductions in simultaneous tension and myoplasmic free Ca2+ were impaired in LCx versus LAD arteries isolated from sedentary but not exercise-trained pigs. In contrast, relaxation in response to the cAMP-dependent vasodilator forskolin (10(-9) to 10(-5) M) and the cGMP-dependent vasodilator sodium nitroprusside (10(-9) to 10(-4) M) was not different in LCx versus LAD arteries of sedentary or exercise-trained animals. These data suggest that chronic occlusion impairs receptor-dependent, cAMP-mediated relaxation; receptor-independent cAMP- and cGMP-mediated relaxation were unimpaired. Importantly, exercise training restores cAMP-mediated relaxation of collateral-dependent coronary arteries.