We have previously reported enhanced Ca²⁺ sensitivity of coronary arteries that are dependent upon collateral circulation for their blood supply. For the current study, we hypothesized that small collateral-dependent arteries would exhibit an enhanced KCl-mediated contractile response attributable to Ca²⁺ sensitization and increased Ca²⁺ channel current. Ameroid constrictors were surgically placed around the left circumflex (LCX) artery of female Yucatan miniature swine. Eight weeks post-operatively, pigs were randomized into sedentary or exercise-trained (treadmill run; 5 days/week; 14 weeks) groups. Small coronary arteries (150-300 mm luminal diameter) were isolated from myocardial regions distal to the collateral-dependent LCX and the nonoccluded left anterior descending arteries. Contractile tension and simultaneous measures of both tension and intracellular free Ca²⁺ levels (fura-2) were measured in response to increasing concentrations of KCl. In addition, whole-cell Ca²⁺ currents were also obtained. Chronic occlusion enhanced contractile responses to KCl and increased Ca²⁺ sensitization in collateral-dependent compared to nonoccluded arteries of both sedentary and exercise-trained pigs. In contrast, smooth muscle cell Ca²⁺ channel current was not altered by occlusion or exercise training. Ca²⁺/calmodulin-dependent protein kinase II (CaMKII; inhibited by KN-93, 0.3-1 mM) contributed to the enhanced contractile response in collateral-dependent arteries of sedentary pigs whereas both CaMKII and Rho-kinase (inhibited by hydroxyfasudil, 30 mM or Y27632, 10 mM) contributed to increased contraction in exercise-trained animals. Taken together, these data suggest that chronic occlusion leads to enhanced contractile responses to KCl in collateral-dependent coronary arteries via increased Ca²⁺ sensitization; a response which is further augmented with exercise training.

中文翻译：

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在运动训练后，增强的 KCl 介导的收缩力和 Ca2+ 敏感性在猪侧支依赖性冠状动脉中持续存在。

我们之前曾报道过冠状动脉的Ca ²⁺敏感性增强，这些冠状动脉的血液供应依赖于侧支循环。对于目前的研究，我们假设小侧支依赖动脉会表现出增强的 KCl 介导的收缩反应，这归因于 Ca ²⁺致敏和增加的 Ca ²⁺通道电流。Ameroid 收缩器通过手术放置在雌性尤卡坦小型猪的左回旋支 (LCX) 动脉周围。术后八周，猪被随机分为久坐或运动训练（跑步机跑步；5 天/周；14 周）组。从侧支依赖 LCX 和未闭塞的左前降支动脉远端的心肌区域中分离出小冠状动脉（150-300 毫米管腔直径）。响应增加的 KCl 浓度测量收缩张力和同时测量张力和细胞内游离 Ca ²⁺水平 (fura-2)。此外，还获得了全细胞 Ca ²⁺电流。慢性闭塞增强对 KCl 的收缩反应并增加 Ca ²⁺与久坐不动和经过运动训练的猪的非闭塞动脉相比，侧支依赖的致敏性。相比之下，平滑肌细胞 Ca ²⁺通道电流不会因闭塞或运动训练而改变。Ca ²⁺ /钙调蛋白依赖性蛋白激酶 II（CaMKII；被 KN-93 抑制，0.3-1 mM）有助于增强久坐猪侧支依赖动脉的收缩反应，而 CaMKII 和 Rho-激酶（被羟基法舒地尔抑制， 30 mM 或 Y27632, 10 mM) 有助于增加运动训练动物的收缩。总之，这些数据表明，慢性闭塞通过增加 Ca ²⁺导致侧支依赖性冠状动脉对 KCl 的收缩反应增强致敏；通过运动训练进一步增强的反应。