细胞外钙离子在兔蛛网膜下腔出血诱导的基底动脉痉挛中的作用。

Role of extracellular Ca2+ in subarachnoid hemorrhage-induced spasm of the rabbit basilar artery.

作者信息

Zuccarello M, Boccaletti R, Tosun M, Rapoport R M

机构信息

Department of Neurosurgery, University of Cincinnati College of Medicine, Ohio 45267-0575, USA.

出版信息

Stroke. 1996 Oct;27(10):1896-902. doi: 10.1161/01.str.27.10.1896.

DOI:10.1161/01.str.27.10.1896

PMID:8841350

Abstract

BACKGROUND AND PURPOSE

The role of extracellular Ca2+ in the maintenance of chronic vasospasm after subarachnoid hemorrhage (SAH) is largely unknown. Indeed, studies thus far have been limited to demonstrations that L-type Ca(2+)-channel antagonists were unable to reverse the spasm. This study tested whether SAH-induced vasospasm is maintained, at least in part. through the influx of extracellular Ca2+ and whether the influx of extracellular Ca2+ occurs through L-type Ca2+ channels and possibly, in addition, through store operated channels (SOCs). Furthermore, as there is considerable evidence in the literature to suggest that the spasm is mediated through endothelin-1 (ET-1) release, we tested whether the Ca2+ dependency of the spasm was consistent with the mediation of the spasm by ET-1.

METHODS

Chronic spasm of the basilar artery was induced in a double SAH rabbit model. Relaxation of SAH-, ET-1-, serotonin-, and KC1-constricted basilar artery in response to Ca(2+)-free solution, verapamil, and Ni2+ was measured in situ with the use of a cranial window.

RESULTS

SAH induced 23% constriction of the basilar artery. Ca(2+)-free solution and 1 mumol/L verapamil reversed the constriction of SAH vessels by 60% and 17%, respectively. In contrast, control vessels challenged with 40 to 50 mmol/L KCl, which induced 34% constriction, relaxed in response to Ca(2+)-free solution and verapamil by 98% and 89%, respectively. In SAH vessels, verapamil followed by 0.1 mmol/L Ni2+, which is known to block SOCs, induced a combined relaxation of 67%. Control vessels challenged with 3 nmol/L ET-1, which induced a magnitude of constriction similar to that of SAH (29%), relaxed in response to Ca(2+)-free solution, verapamil, and verapamil plus Ni2+ by 69%, 20%, and 50%, respectively (P > .05) versus respective values in SAH vessels). In contrast, control vessels challenged with 2 to 8 mumol/L serotonin, which induced a magnitude of constriction similar to those of SAH and ET-1 (22%), completely relaxed in response to Ca(2+)-free solution and verapamil.

CONCLUSIONS

These results demonstrate that the maintenance of chronic spasm in the two-hemorrhage rabbit model after SAH is due to smooth muscle cell contractile mechanisms partly dependent on the influx of extracellular Ca2+. The influx of extracellular Ca2+ results from the opening of L-type Ca2+ channels and an additional channel or channels. We speculate that the L-type Ca2+ channel-independent influx of extracellular Ca2+ results from the opening of SOCs. The Ca(2+)-dependent characteristics of the spasm likely reflect the mediation of the spasm by ET-1.

摘要

背景与目的

蛛网膜下腔出血（SAH）后细胞外Ca2+在维持慢性血管痉挛中的作用尚不清楚。事实上，迄今为止的研究仅限于表明L型Ca(2+)通道拮抗剂无法逆转痉挛。本研究测试了SAH诱导的血管痉挛是否至少部分是通过细胞外Ca2+的内流维持的，以及细胞外Ca2+的内流是否通过L型Ca2+通道发生，此外还可能通过储存操纵通道（SOCs）发生。此外，由于文献中有大量证据表明痉挛是通过内皮素-1（ET-1）释放介导的，我们测试了痉挛的Ca2+依赖性是否与ET-1介导的痉挛一致。

方法

在双SAH兔模型中诱导基底动脉慢性痉挛。使用颅窗原位测量SAH、ET-1、5-羟色胺和KCl收缩的基底动脉对无Ca(2+)溶液、维拉帕米和Ni2+的舒张反应。

结果

SAH诱导基底动脉收缩23%。无Ca(2+)溶液和1μmol/L维拉帕米分别使SAH血管的收缩逆转60%和17%。相比之下，用40至50mmol/L KCl刺激的对照血管收缩34%，对无Ca(2+)溶液和维拉帕米的舒张反应分别为98%和89%。在SAH血管中，维拉帕米之后加入已知可阻断SOCs的0.1mmol/L Ni2+，诱导的联合舒张为67%。用3nmol/L ET-1刺激的对照血管收缩程度与SAH相似（29%），对无Ca(2+)溶液、维拉帕米和维拉帕米加Ni2+的舒张反应分别为69%、20%和50%（与SAH血管中的相应值相比，P>.05）。相比之下，用2至8μmol/L 5-羟色胺刺激的对照血管收缩程度与SAH和ET-1相似（22%），对无Ca(2+)溶液和维拉帕米完全舒张。

结论

这些结果表明，SAH后双出血兔模型中慢性痉挛的维持是由于平滑肌细胞收缩机制部分依赖于细胞外Ca2+的内流。细胞外Ca2+的内流是由L型Ca2+通道和一个或多个其他通道的开放引起的。我们推测细胞外Ca2+不依赖L型Ca2+通道的内流是由SOCs的开放引起的。痉挛的Ca(2+)依赖性特征可能反映了ET-1对痉挛的介导作用。