Aerobic exercise-induced inhibition of PKCα/CaV1.2 pathway enhances the vasodilation of mesenteric arteries in hypertension
Aerobic exercise-induced inhibition of PKCα/CaV1.2 pathway enhances the vasodilation of mesenteric arteries in hypertension
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DOI：
10.1016/j.abb.2019.108191
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发表时间：
2019-12-15
影响因子：
3.9
通讯作者：
Shi, Lijun
中科院分区：
文献类型：
--
作者：
Chen, Yu;Zhang, Yanyan;Shi, Lijun
有规律的运动被认为是通过改善血管平滑肌细胞（VSMCs）功能来控制高血压的一种非药物疗法。潜在的机制尚不清楚。细胞膜上的L型电压依赖性Ca ~（2+）通道（Ca（V）1.2）和VSMC的PKC α是血管张力的关键调节剂。PKC α在高血压期间过度活化并集中在表面膜上。研究有氧运动对自发性高血压大鼠（SHR）肠系膜动脉平滑肌细胞PKC α和Ca（V）1.2的影响。将SHR和WKY大鼠随机分为安静组（SHR-SED和WKY-SED）和运动训练组（SHR-EX和WKY-EX）。运动组进行为期12周的中等强度（18-20 m/min）跑台训练。肠系膜动脉的机械和功能特性进行了评价。运动降低了SHR-EX和WKY-EX的体重和收缩压。PDBu（PKC激活剂）和BayK 8644（Ca（V）1.2激动剂）引起血管收缩，而Go 6976（PKC α抑制剂）和硝苯地平（Ca（V）1.2阻断剂）引起血管环舒张。在SHR中，运动使血管对这些激活剂和抑制剂的敏感性增加正常化。硝苯地平大大抑制PDBu-induced血管收缩。与Go 6976孵育后，PDBu和硝苯地平的作用均被显著抑制。在膜片钳研究中，PDBu增加和Go 6976降低Ca（V）1.2电流密度。运动改善了PDBu和Go 6976在SHR中的反应。免疫荧光染色显示，运动训练可减轻高血压引起的PKC α和Ca（V）1.2 α（1C）亚单位在VSMCs共定位率的增加。这些数据表明，高血压增强PKC α/Ca（V）1.2途径诱导的肠系膜动脉收缩，这种病理增强被有氧运动训练抑制。
Regular exercise is regarded as a nonpharmacological therapy for controlling hypertension by improving the function of vascular smooth muscle cells (VSMCs). The underlying mechanism is unclear. L-type-voltage-dependent Ca2+ channel (Ca(V)1.2) on the plasma membrane and PKC alpha of VSMCs are pivotal modulators of vascular tone. PKC alpha is hyperactivated and concentrated at the surface membrane during hypertension. This study investigated the effects of aerobic exercise on the PKC alpha and Ca(V)1.2 in mesenteric arterial smooth muscle cells from spontaneously hypertensive rats (SHRs). SHRs and Wistar-Kyoto (WKY) rats were randomly assigned into sedentary groups (SHR-SED and WKY-SED) and exercise training groups (SHR-EX and WKY-EX). Exercise groups were performed a 12-week moderate-intensity (18-20 m/min) treadmill training. Mesenteric arterial mechanical and functional properties were evaluated. Exercise reduced body weight and systolic blood pressure in both SHR-EX and WKY-EX. PDBu (PKC activator) and BayK 8644 (Ca(V)1.2 agonist) elicited vasoconstriction, while Go6976 (PKC alpha inhibitor) and nifedipine (Ca(V)1.2 blocker) induced vasodilation of the vessel rings. In SHRs, exercise normalized the increased vascular sensitivity to these activators and inhibitors. Nifedipine greatly suppressed PDBu-induced vasoconstriction. Upon incubation with Go6976, the effects of both PDBu and nifedipine were markedly suppressed. In patch-clamp studies, PDBu increased and Go6976 decreased the Ca(V)1.2 current density. Exercise ameliorated the responses of both PDBu and Go6976 in SHRs. Immunofluorescence staining suggested that exercise training alleviated the hypertension-induced increase of colocalization rate of PKC alpha and Ca(V)1.2 alpha(1C) subunit in VSMCs. These data indicate that hypertension enhanced PKC alpha/Ca(V)1.2 pathway-induced constriction of mesenteric arteries, and this pathological enhancement is inhibited by aerobic exercise training.