Longer muscle lengths recapitulate force suppression in swine carotid artery.
Longer muscle lengths recapitulate force suppression in swine carotid artery.
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较长的肌肉长度再现了猪颈动脉的力抑制。
DOI：
10.1152/ajpheart.00775.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Han,Shaojie
中科院分区：
文献类型：
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作者：
Rembold,ChristopherM;Meeks,MelissaK;Ripley,MarciaL;Han,Shaojie
环核苷酸可以松弛动脉平滑肌而不减少肌球蛋白调节轻链（MRLC）磷酸化，这一过程称为力抑制。平滑肌收缩力也取决于组织长度。目前尚不清楚组织长度如何影响力抑制。猪颈动脉环在不同长度下平衡（作为Lo的一部分，力发展的最佳长度）。然后在有或没有毛喉素诱导的松弛的收缩激活期间将它们冷冻。然后分析冷冻组织匀浆的Ser 19-MRLC磷酸化和Ser 16-热休克蛋白20（HSP 20）磷酸化（HSP 20是提出的力抑制介质）。需要较高的MRLC磷酸化值诱导组胺收缩在较长的组织长度。在1.4Lo时，仅用组胺刺激观察到的力对MRLC磷酸化的依赖性向右移动，这一反应类似于在1.0Lo时力抑制期间观察到的反应。在1.4L0单独组胺刺激下，力对MRLC磷酸化的依赖性发生显著变化，但与HSP 20磷酸化的增加无关。在组胺刺激的组织中加入1.4Lo的毛喉素诱导了与增加的HSP 20磷酸化和减少的MRLC磷酸化相关的松弛，即，没有额外的力抑制。在较短的组织长度（0.6Lo），依赖于MRLC磷酸化与组胺刺激单独的力是陡峭的，类似于在正常的收缩激活在1.0Lo的反应。在0.6Lo下增加毛喉素诱导力抑制。与较短的组织长度相比，较长的组织长度猪颈动脉对组胺浓度的敏感性更大，这表明恢复最佳组织长度的生理机制。这些数据表明，较长的组织长度诱导了一种力抑制样状态，这种状态1）与毛喉素无关，2）与HSP 20磷酸化无关。需要进一步的研究来确定这种长度依赖性机制。
Cyclic nucleotide can relax arterial smooth muscle without reductions in myosin regulatory light chain (MRLC) phosphorylation, a process termed force suppression. Smooth muscle contractile force also depends on tissue length. It is not known how tissue length affects force suppression. Swine carotid artery rings were equilibrated at various lengths (as a fraction ofLo, the optimal length for force development). They were then frozen during contractile activation with or without forskolin-induced relaxation. Frozen tissue homogenates were then analyzed for Ser19-MRLC phosphorylation and Ser16-heat shock protein 20 (HSP20) phosphorylation (HSP20 is the proposed mediator of force suppression). Higher values of MRLC phosphorylation were required to induce a histamine contraction at longer tissue lengths. At 1.4Lo, the dependence of force on MRLC phosphorylation observed with histamine stimulation alone was shifted to the right, a response similar to that observed during force suppression at 1.0Lo. The rightward shift in the dependence of force on MRLC phosphorylation seen with histamine stimulation alone at 1.4Lowas not associated with increased HSP20 phosphorylation. Addition of forskolin to histamine-stimulated tissues at 1.4Loinduced a relaxation associated with increased HSP20 phosphorylation and reduced MRLC phosphorylation, i.e., there was no additional force suppression. At shorter tissue lengths (0.6Lo), the dependence of force on MRLC phosphorylation with histamine stimulation alone was steep, a response similar to that observed during normal contractile activation at 1.0Lo. Addition of forskolin induced force suppression at 0.6Lo. The sensitivity of swine carotid to the concentration of histamine was greater at longer tissue lengths compared with shorter tissue lengths, suggesting a physiological mechanism to restore optimal tissue length. These data suggest that longer tissue lengths induced a force suppression-like state that was1) not additive with forskolin and2) not associated with HSP20 phosphorylation. Further research is required to determine this length-dependent mechanism.