RESUMO
The herbal extract Angelica gigas (AG) has been applied as a vasodilating agent for patients suffering from vascular diseases for many years; however, the underlying mechanism has not been fully elucidated. The present study hypothesized that the antivasoconstrictive effect of AG may be effective in the treatment of abnormal coldmediated vasospasms that occur in Raynaud's phenomenon (RP). The effect of AG on the activity of ras homolog gene family member A (RhoA) was investigated in coldexposed vascular cells. Vascular cells were pretreated to AG, followed by a warm (37ËC) or cold (25ËC) incubation for 30 min and investigated with western blotting, ELISA and confocal microscopy. Cold treatment induced the activation of RhoA in pericytes and vascular endothelial cells, however this was reduced by treatment with AG. Furthermore, AG treatment reduced the endothelin1 (ET1)mediated RhoA activation in pericytes; however, coldinduced ET1 production by vascular endothelial cells was not affected by treatment with AG. In addition, AG treatment suppressed the formation of stress fibers and focal adhesion complexes, and the coldinduced phosphorylation of focal adhesion kinase, protooncogene tyrosineprotein kinase Src and extracellular signalrelated kinase. Therefore, AG treatment demonstrated an ability to reduce coldinduced RhoA activation in pericytes and vascular endothelial cells, and attenuated ET1mediated RhoA activation in pericytes. In conclusion, the present study indicated that AG may be useful for the treatment of RP.