Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats
Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats
复制标题
自发性高血压大鼠肠系膜动脉中 Cav1.2 通道的运动强度依赖性逆转和不良重塑
DOI：
10.1038/hr.2015.56
复制
发表时间：
2015-10-01
影响因子：
5.4
通讯作者：
Shi, Lijun
中科院分区：
文献类型：
--
作者：
Chen, Yu;Zhang, Hanmeng;Shi, Lijun
运动可被视为治疗高血压的一种药物，因此“剂量”（强度/运动量）至关重要。血管平滑肌细胞质膜上的L型电压门控Ca²⁺（Ca₍ᵥ₎1.2）通道在调节血管张力方面具有关键作用，Ca₍ᵥ₎1.2通道的上调是高血压的一个标志性特征。本研究探讨了不同强度运动对自发性高血压大鼠（SHRs）肠系膜动脉（MAs）中Ca₍ᵥ₎1.2通道重塑的有益和不良影响。为SHRs设立了中等强度（SHR - M，18 - 20米/分钟）和高强度（SHR - H，26 - 28米/分钟）有氧运动训练组，持续8周（每天1小时，每周5天）。选用年龄匹配的久坐不动的SHRs和血压正常的京都大鼠（WKY）作为对照。评估了肠系膜动脉的力学和功能特性。与久坐的SHRs相比，中等强度运动训练使这些大鼠的收缩压和心率降低。BayK 8644和硝苯地平分别在肠系膜动脉环中诱导血管收缩和剂量依赖性血管舒张。中等强度运动显著抑制了SHRs的MAs中BayK 8644诱导的血管收缩增加、对硝苯地平的组织敏感性、Ca₍ᵥ₎1.2通道电流密度以及Ca₍ᵥ₎1.2α1C亚基蛋白表达。然而，高强度运动训练加剧了Ca₍ᵥ₎1.2通道所有这些与高血压相关的功能和分子改变。这些结果表明，中等强度的有氧训练可作为一种药物，有效逆转高血压中Ca₍ᵥ₎1.2通道的重塑，恢复MAs的血管功能，但高强度运动会加剧Ca₍ᵥ₎1.2通道的不良重塑并恶化血管功能。
Exercise can be regarded as a drug for treating hypertension, and the 'dosage' (intensity/volume) is therefore of great importance. L-type voltage-gated Ca2+ (Ca(v)1.2) channels on the plasma membrane of vascular smooth muscle cells have a pivotal role in modulating the vascular tone, and the upregulation of Ca(v)1.2 channels is a hallmark feature of hypertension. The present study investigated the beneficial and adverse effects of exercise at different intensities on the remodeling of the Ca(v)1.2 channel in mesenteric arteries (MAs) of spontaneously hypertensive rats (SHRs). Moderate-(SHR-M, 18-20 m min(-1)) and high-intensity (SHR-H, 26-28 m min(-1)) aerobic exercise training groups were created for SHRs and lasted for 8 weeks (1 h per day, 5 d per week). Age-matched sedentary SHRs and normotensive Wistar-Kyoto rats (WKY) were used as controls. The mesenteric arterial mechanical and functional properties were evaluated. Moderate-intensity exercise training induced a lower systolic blood pressure and heart rate in these rats compared with sedentary SHRs. BayK 8644 and nifedipine induced vasoconstriction and dose-dependent vasorelaxation, respectively, in the mesenteric arterial rings. Moderate-intensity exercise significantly suppressed the increase in BayK 8644-induced vasoconstriction, tissue sensitivity to nifedipine, Ca(v)1.2 channel current density and Ca(v)1.2 alpha 1C-subunit protein expression in MAs from SHRs. However, high-intensity exercise training aggravated all of these hypertension-associated functional and molecular alterations of Ca(v)1.2 channels. These results indicate that moderate-intensity aerobic training may act as a drug and effectively reverse the remodeling of Ca(v)1.2 channels in hypertension to restore the vascular function in MAs, but that high-intensity exercise exaggerates the adverse remodeling of Ca(v)1.2 channels and worsens the vascular function.