The screening of novel inhibitors for Ca²⁺-independent abnormal contraction of vascular smooth muscle which have similar inhibitory effects to eicosapentaenoic acid

Abstract

We previously identified sphingosylphosphorylcholine (SPC) and Fyn as upstream signal molecules of Rho-kinase-mediated Ca²⁺-independent abnormal contraction of vascular smooth muscle (VSM) and found that eicosapentaenoic acid (EPA) can selectively inhibit such abnormal events without affecting Ca²⁺-dependent normal VSM contraction by blocking the translocation of Fyn to plasma membrane. Moreover, we reported that EPA was clinically and highly effective in preventing vasospasm after subarachnoid hemorrhage. However, EPA is limited to oral administration and thus unsuitable for clinically serious patients unable to ingest orally. We therefore screened novel compounds which could inhibit Ca²⁺-independent abnormal VSM contraction and could substitute for EPA. Tension study of VSM showed that several compounds inhibited SPC-induced abnormal VSM contraction, which was comparable to the effects of EPA. These results suggest that these newly found compounds would be the candidates for novel therapeutic drugs for vasospasm which could substitute for EPA. [J Physiol Sci. 2006;56 Suppl:S67]