title: Cilostazol strengthens the endothelial barrier of postcapillary venules from the rat mesentery in situ.
abstract: OBJECTIVE
  Although cilostazol, a phosphodiesterase 3 inhibitor, has been suggested to strengthen the endothelial barrier using cultured endothelial monolayers, its effect has not been tested in vivo. We, therefore, investigated effects of cilostazol on barrier properties of postcapillary venules of the rat in situ.
  
  
  METHODS
  Cilostazol was administered to the rats through oral gavage at 4 hours before the measurements. The hydraulic permeability (L(p)) and the effective osmotic pressure (σΔπ), molecular sieving properties of microvascular walls, were estimated in single mesenteric postcapillary venules by a micro-occlusion technique, first during control perfusion and then in the presence of histamine.
  
  
  RESULTS
  When the vessels were inflamed with histamine, cilostazol attenuated a transient increase in L(p) and prevented σΔπ from falling. Furthermore, it reduced baseline L(p) under a control state.
  
  
  CONCLUSIONS
  Cilostazol appears to tighten the endothelial barrier in situ, at least in part by inhibiting the cAMP-degrading enzyme in the endothelium.
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan National Hospital Organization, Kanagawa National Hospital, Pulmonary and Thoracic Surgery, Kanagawa, Japan.
authors.forename: Yasoo
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan Japan Science and Technology Agency, Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan Department of Pediatrics, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Takenouchi
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan Japan Science and Technology Agency, Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan Japan Science and Technology Agency, Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project, Tokyo, Japan myk30@z5.keio.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kajimura
mesh_terms: D000818:Animals; D000077407:Cilostazol; D004730:Endothelium, Vascular / Q000187:drug effects*; D006439:Hemodynamics; D006632:Histamine / Q000737:chemistry; D007249:Inflammation; D008297:Male; D008643:Mesentery / Q000473:pathology*; D008833:Microcirculation; D009997:Osmotic Pressure; D010539:Permeability; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D006632:Histamine; D000077407:Cilostazol
keywords: Microvascular permeability; antiplatelet drugs; phosphodiesterase 3