抄録
Rho-kinase (ROK)-mediated Ca2+-independent abnormal contraction of vascular smooth muscle (VSM) plays an essential role in the pathophysiology of the vasospasm which causes vascular diseases. As an important signaling molecule of vasospasm, we previously identified sphingosylphosphorylcholine (SPC), which activated ROK through the activation of Src family tyrosine kinase (Src-TK) and induced Ca2+-independent contraction of VSM. Moreover, we found that eicosapentaenoic acid (EPA) can selectively inhibit such abnormal events without affecting Ca2+-dependent normal contraction of VSM. However, EPA is limited to oral administration and thus unsuitable for clinically serious patients unable to ingest orally. We therefore screened the new compounds which are capable to be administrated intravenously that could substitute for EPA. Tension study of VSM showed that several compounds inhibited the SPC-induced abnormal contraction of VSM, and their inhibitory effects were comparable to EPA's. These results suggest that newly found compounds would be the candidates for novel therapeutic drugs capable to be administrated intravenously for vasospasm which could substitute for EPA. [J Physiol Sci. 2007;57 Suppl:S66]
