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-HT(2A) receptor, and sarpogrelate, a selective 5-HT(2A) 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-HT(2A) receptor and the Rho-kinase pathway.
Nishihira
K
K
Division of Circulatory and Body Fluid Regulation, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan.
Yamashita
A
A
Tanaka
N
N
Moriguchi-Goto
S
S
Imamura
T
T
Ishida
T
T
Kawashima
S
S
Yamamoto
R
R
Kitamura
K
K
Asada
Y
Y
D000818:Animals; D050197:Atherosclerosis; D005263:Femoral Artery; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D011817:Rabbits; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin / Q000494:pharmacology*; D017539:Tunica Intima / Q000166:cytology / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*; D054460:rho-Associated Kinases / Q000378:metabolism
D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D054460:rho-Associated Kinases