title: Sarpogrelate dilates cerebral arteries in the absence of exogenous serotonin.
abstract: Vasoconstriction of arteries induced by serotonin (5-hydroxytryptamine: 5-HT) is mediated by 5-HT2A and 5-HT1B receptors localized on smooth muscle. The present study investigated the impact of sarpogrelate, a 5-HT2A receptor antagonist, on cerebral artery diameter in the presence and absence of exogenous 5-HT. Diameter measurements were obtained in vitro from rabbit cerebral arteries pressurized to 60 mmHg. In the absence of 5-HT, arteries exhibiting pressure-induced myogenic tone dilated to sarpogrelate in a concentration-dependent manner (half maximal inhibitory concentration [IC50] ≈ 2.3 μM). In a separate experimental series, exogenous application of 5-HT (0.01 μM) caused further constriction of myogenically active arteries, decreasing cerebral artery diameter by an additional 25%. In the presence of 5-HT, sarpogrelate caused concentration-dependent vasodilation (IC50 ≈ 2.3 μM) that was similar to that observed in the absence of exogenous 5-HT. Dilation induced by sarpogrelate was not affected by physical removal of the endothelium or inhibition of nitric oxide synthase with Nω-nitro L-arginine. The highest concentration of sarpogrelate (100 μM) induced near maximal dilation, comparable to dilation induced by the L-type voltage-dependent calcium channel antagonist diltiazem. These findings suggest that in rabbit cerebral arteries, sarpogrelate has direct vasodilator effects on vascular smooth muscle.
authors.affiliation: Department of Neurosurgery, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Kawamura
authors.forename: Masanori
authors.initials: M
authors.lastname: Ishiguro
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagamine
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin; D004110:Diltiazem