Tosaka M, Okajima F, Hashiba Y, Saito N, Nagano T, Watanabe T, Kimura T, Sasaki T
Department of Neurosurgery, Gunma University School of Medicine, the Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Stroke. 2001 Dec 1;32(12):2913-9. doi: 10.1161/hs1201.099525.
Sphingosine 1-phosphate (S1P) is a platelet-derived bioactive lipid that exerts a variety of biological responses, including vasocontraction. To understand the involvement of S1P in cerebral vasospasm, we investigated the effect of S1P on vasocontraction of the canine basilar artery in vitro and in vivo.
We recorded isometric tension in basilar arterial rings from dogs in vitro and estimated time-course changes in the diameter of canine basilar arteries and the S1P concentration in cerebrospinal fluid (CSF) by angiography and radioreceptor assays, respectively, after administering S1P into the cisterna magna. Changes in the supernatant S1P concentration during clot formation were monitored by using the in vitro subarachnoid hemorrhage model, in which blood is mixed with CSF.
At concentrations ranging between 100 nmol/L and 10 micromol/L, S1P induced a dose-dependent contraction of the basilar artery in vitro. This effect was significantly inhibited by Y-27632, a highly selective Rho-kinase inhibitor. The administration of S1P into the CSF induced a 60% to 70% decrease in the arterial diameter within 15 minutes, and vasocontraction continued for 2 days thereafter. The concentration of S1P in the supernatant during clot formation in vitro reached approximately 300 nmol/L.
S1P induces vasocontraction in the canine basilar artery in vitro and in vivo, possibly through a mechanism involving activation of the Rho/Rho-kinase pathway. Thus, S1P might be considered as a novel spasmogenic substance involved in cerebral vasospasm after subarachnoid hemorrhage.
1-磷酸鞘氨醇（S1P）是一种血小板衍生的生物活性脂质，可引发多种生物学反应，包括血管收缩。为了解S1P在脑血管痉挛中的作用，我们在体外和体内研究了S1P对犬基底动脉血管收缩的影响。
我们在体外记录犬基底动脉环的等长张力，并分别通过血管造影和放射受体分析评估在将S1P注入小脑延髓池后犬基底动脉直径的时间进程变化以及脑脊液（CSF）中S1P的浓度。使用体外蛛网膜下腔出血模型（将血液与CSF混合）监测凝血形成过程中上清液S1P浓度的变化。
在100 nmol/L至10 μmol/L的浓度范围内，S1P在体外诱导基底动脉剂量依赖性收缩。这种作用被高度选择性的Rho激酶抑制剂Y-27632显著抑制。将S1P注入CSF在15分钟内导致动脉直径减小60%至70%，此后血管收缩持续2天。体外凝血形成过程中上清液中S1P的浓度达到约300 nmol/L。
S1P在体外和体内均可诱导犬基底动脉血管收缩，可能是通过涉及Rho/Rho激酶途径激活的机制。因此，S1P可能被视为蛛网膜下腔出血后参与脑血管痉挛的一种新型致痉物质。
