Serotonin induces vasoconstriction of smooth muscle cell-rich neointima through 5-hydroxytryptamine2A receptor in rabbit femoral arteries

Background: Smooth muscle cell (SMC)-rich intima is a morphological feature of atherosclerotic lesions that is observed in eroded plaque and spastic arteries. Arteries with SMC-rich intima are susceptible to vasoconstriction or vasospasm against some vasoactive agents. Objective: The present study evaluates the contribution of SMC-rich intima to thrombogenic vasoconstriction. Methods: We established SMC-rich neointima by damaging rabbit femoral arteries using balloons and then measured the isometric tension of the femoral strips against 5-hydroxytryptamine (5-HT), adenosine diphosphate, adenosine triphosphate and thrombin. Results: Among these agents, only 5-HT induced a hypercontractile response of the injured arteries with SMC-rich neointima, compared with non-injured arteries. Smooth muscle cells of both the neointima and media expressed 5-HT2A receptor, and sarpogrelate, a selective 5-HT2A receptor antagonist significantly inhibited the hypercontraction. Furthermore, 5-HT induced contraction of separated neointima and hypercontraction of separated media compared with non-injured media. Sarpogrelate and fasudil, a specific Rho-kinase inhibitor, significantly suppressed such contraction of both the neointima and media of injured arteries. Conclusions: These results suggest that 5-HT plays a crucial role in thrombogenic vasoconstriction, and that SMC-rich intima as well as media directly contributes to the hypercontractile response of atherosclerotic vessels through the 5-HT2A receptor and the Rho-kinase pathway.