Differential regulation of L-type Ca2+ channels in cerebral and mesenteric arteries after simulated microgravity in rats and its intervention by standing
Differential regulation of L-type Ca2+ channels in cerebral and mesenteric arteries after simulated microgravity in rats and its intervention by standing
复制标题
模拟微重力大鼠脑动脉和肠系膜动脉L型Ca2+通道的差异调节及站立干预
DOI：
10.1152/ajpheart.01229.2006
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发表时间：
2007-07-01
影响因子：
4.8
通讯作者：
Xie, Man-Jiang
中科院分区：
文献类型：
--
作者：
Xue, Jun-Hui;Zhang, Li-Fan;Xie, Man-Jiang
本研究旨在阐明模拟微重力是否会引起大脑和肠系膜动脉中 L 型 Ca2+ 通道 (Ca-L) 的电流和蛋白表达的差异变化，以及这些变化是否可以通过每日短时暴露 -G(x) 来预防。尾部悬吊[后肢卸载 (HU)] 3 天和 28 天用于模拟短期和中期微重力引起的失调效应。每天站立 (STD) 1 小时用于提供 -G(x) 作为对策。全细胞膜片钳实验显示，从接受 HU 的大鼠脑动脉中分离出的血管平滑肌细胞 (VSMC) 的 Ca-L 电流密度增加，而来自肠系膜动脉的 VSMC 减少。蛋白质印迹分析显示，仅在 HU 28 天后，大脑和小肠系膜动脉 VSMC 中的 Ca-L 通道蛋白表达分别显着增加和减少。 STD 1 h/天不能阻止脑动脉 VSMC 中 Ca-L 电流密度的增加，但可以完全（3 天内）和部分（28 天内）阻止小肠系膜动脉 VSMC 中 Ca-L 电流密度的降低。与Ca-L电流的变化一致，STD 1小时/天并没有阻止脑血管肌细胞中Ca-L表达的增加，但确实阻止了接受28天HU的肠系膜动脉VSMC中Ca-L表达的减少。这些数据表明，模拟微重力分别上调和下调大脑和后躯 VSMC 中 Ca-L 的电流和表达。 STD 1 小时/天差异抵消了 HU 大鼠大脑和后肢动脉 VSMC 中 Ca-L 功能和表达的变化，表明间歇性人工重力预防飞行后心血管功能失调的潜在机制的复杂性，需要进一步阐明。
This study was designed to clarify whether simulated microgravity can induce differential changes in the current and protein expression of the L-type Ca2+ channel (Ca-L) in cerebral and mesenteric arteries and whether these changes can be prevented by daily short-duration -G(x) exposure. Tail suspension [hindlimb unloading (HU)] for 3 and 28 days was used to simulate short- and medium-term microgravity-induced deconditioning effects. Standing (STD) for 1 h/day was used to provide -G(x) as a countermeasure. Whole cell patch-clamp experiments revealed an increase in current density of Ca-L of vascular smooth muscle cells (VSMCs) isolated from cerebral arteries of rats subjected to HU and a decrease in VSMCs from mesenteric arteries. Western blot analysis revealed a significant increase and decrease of Ca-L channel protein expression in cerebral and small mesenteric arterial VSMCs, respectively, only after 28 days of HU. STD for 1 h/day did not prevent the increase of Ca-L current density in cerebral arterial VSMCs, but it prevented completely (within 3 days) and partially (28 days) the decrease of Ca-L current density in small mesenteric arterial VSMCs. Consistent with the changes in Ca-L current, STD for 1 h/day did not prevent the increase of Ca-L expression in cerebrovascular myocytes but did prevent the reduction of Ca-L expression in mesenteric arterial VSMCs subjected to 28 days of HU. These data indicate that simulated microgravity up- and downregulates the current and expression of Ca-L in cerebral and hindquarter VSMCs, respectively. STD for 1 h/day differentially counteracted the changes of Ca-L function and expression in cerebral and hindquarter arterial VSMCs of HU rats, suggesting the complexity of the underlying mechanisms in the effectiveness of intermittent artificial gravity for prevention of postflight cardiovascular deconditioning, which needs further clarification.