title: Effect of sarpogrelate hydrochloride, a 5-hydroxytryptamine2 receptor antagonist, on allograft arteriosclerosis after aortic transplantation in rats.
abstract: BACKGROUND
  Sarpogrelate hydrochloride, a 5-hydroxytryptamine2 receptor antagonist, is known to prevent serotonin-induced neointimal hyperplasia. We examined the effect of this agent on allograft arteriosclerosis in a rat model of aortic transplantation.
  
  
  METHODS
  Rats were given an aortic isograft or allograft and oral administration of either saline vehicle alone or 20mg/kg daily of sarpogrelate for 8 weeks. The grafts were then harvested, and the lumen diameter and the thickness of the intima and media were measured. Comparisons were made between measurement results in isografts and allografts from rats treated and not treated with sarpogrelate. Immunohistochemistry assessments were used to detect expression of serotonin in graft specimens.
  
  
  RESULTS
  For both allografts and isografts, significantly less intimal thickening was observed in specimens from rats given sarpogrelate compared with rats given saline. Sarpogrelate had no effect on medial thickening in either graft type. Serotonin was detected in allografts from rats given saline alone but not in allografts from rats given sarpogrelate or in isografts.
  
  
  CONCLUSIONS
  Sarpogrelate hydrochloride may mitigate arteriosclerosis in allografts. Platelet aggregation and serotonin may be correlated with intimal thickening associated with chronic rejection.
authors.affiliation: Department of Surgery, Keio University School of Medicine, 35, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Watada
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Harada
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsubara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Obara
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Ando
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D064591:Allografts; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D016377:Organ Transplantation; D051381:Rats; D011917:Rats, Inbred Lew; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D013386:Succinates / Q000494:pharmacology*
chemical_list: D005343:Fibrinolytic Agents; D058830:Serotonin 5-HT2 Receptor Antagonists; D013386:Succinates; C064294:sarpogrelate
keywords: 5-HT; 5-HT(2)R; 5-hydroxytryptamine; 5-hydroxytryptamine(2) receptor; Allograft arteriosclerosis; Qint; Qmed; Rat; Sarpogrelate hydrochloride; TBS; Transplantation; Tris buffered saline; VSMC; relative thickness of intima, calculated as: intima/(lumen+intima+media)×100; relative thickness of media, calculated as: media/(lumen+intima+media)×100; vascular smooth muscle cells