Yasoo Sugiura1, Takayuki Morikawa2, Toshiki Takenouchi3, Makoto Suematsu2, Mayumi Kajimura4. 1. Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan National Hospital Organization, Kanagawa National Hospital, Pulmonary and Thoracic Surgery, Kanagawa, Japan. 2. 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. 3. Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan Department of Pediatrics, School of Medicine, Keio University, Tokyo, Japan. 4. 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.
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. CONCLUSION: Cilostazol appears to tighten the endothelial barrier in situ, at least in part by inhibiting the cAMP-degrading enzyme in the endothelium.
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. CONCLUSION:Cilostazol appears to tighten the endothelial barrier in situ, at least in part by inhibiting the cAMP-degrading enzyme in the endothelium.
Authors: Min Hyung Lee; Sang Uk Kim; Dong Hoon Lee; Young Il Kim; Chul Bum Cho; Seung Ho Yang; Il Sup Kim; Jae Taek Hong; Jae Hoon Sung; Sang Won Lee Journal: J Cerebrovasc Endovasc Neurosurg Date: 2016-09-30