Sphingosine 1-Phosphate Contracts Canine Basilar Arteries In Vitro and In Vivo Possible Role in Pathogenesis of Cerebral Vasospasm

摘要: Background and Purpose — Sphingosine 1-phosphate (S1P) is a platelet-derived bioactive lipid that exerts variety of biological responses, including vasocontraction. To understand the involvement S1P in cerebral vasospasm, we investigated effect on vasocontraction canine basilar artery vitro vivo. Methods We recorded isometric tension arterial rings from dogs estimated time-course changes diameter arteries concentration cerebrospinal fluid (CSF) by angiography radioreceptor assays, respectively, after administering into cisterna magna. Changes supernatant during clot formation were monitored using subarachnoid hemorrhage model, which blood mixed with CSF. Results At concentrations ranging between 100 nmol/L 10 μmol/L, induced dose-dependent contraction vitro. This was significantly inhibited Y-27632, highly selective Rho-kinase inhibitor. The administration CSF 60% to 70% decrease within 15 minutes, continued for 2 days thereafter. reached ≈300 nmol/L. Conclusions induces vivo, possibly through mechanism involving activation Rho/Rho-kinase pathway. Thus, might be considered as novel spasmogenic substance involved vasospasm hemorrhage.