Sphingosine 1-phosphate contracts canine basilar arteries in vitro and in vivo - Possible role in pathogenesis of cerebral vasospasm

Background and Purpose-Sphingosine 1-phosphate (S1P) is a platelet-derived bioactive lipid that exerts a variety of biological responses, including, v asocontraction. 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. Methods-We recorded isometric tension in basilar arterial rings from dogs i n vitro and estimated time-course changes in the diameter of canine basilar arteries and the S1P concentration in cerebrospinal fluid (CSF) by angiogr aphy and radioreceptor assays, respectively, after administering S1P into t he cisterna magna. Changes in the supernatant S1P concentration during clot formation were monitored by using the in vitro subarachnoid hemorrhage mod el, in which blood is mixed with CSF. Results-At concentrations ranging between 100 nmol/L and 10 mu mol/L, S1P i nduced a dose-dependent contraction of the basilar artery in vitro. This ef fect was significantly inhibited by Y-27632, a highly selective Rho-kinase inhibitor. The administration of S1P into the CSF induced a 60% to 70% decr ease in the arterial diameter within 15 minutes, and vasocontraction contin ued for 2 days thereafter. The concentration of SIP in the supernatant duri ng clot formation in vitro reached approximate to 300 nmol/L. Conclusions-S1P induces vasocontraction in the canine basilar artery in vit ro and in vivo, possibly through a mechanism involving activation of the Rh o/Rho-kinase pathway. Thus, S1P might be considered as a novel spasmogenic substance involved in cerebral vasospasm after subarachnoid hemorrhage.