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 ( Lp) 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 Lp and prevented σΔπ from falling. Furthermore, it reduced baseline Lp 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.