INHIBITION OF SHEAR STRESS-INDUCED PLATELET-AGGREGATION BY CILOSTAZOL, A SPECIFIC INHIBITOR OF CGMP-INHIBITED PHOSPHODIESTERASE, IN-VITRO AND EX-VIVO

razol-5-yl)-butoxy]-3,4-dihydro-2(1H)-quinolinone) selectively inhibit s cGMP-inhibited phosphodiesterase(PDE3) and is a potent inhibitor of platelet aggregation induced by various agonists. Effect of cilostazol on shear stress-induced human platelet aggregation(SIPA) was examined in vitro and ex vivo. Cilostazol inhibited SIPA dose-dependently in v itro. The IC50 value of cilostazol for inhibition of SIPA was 15 +/- 2 .6 mu M(m +/- SE, n=5), which was very similar to that(12.5 +/- 2.1 mu M) for inhibition of ADP-induced platelet aggregation. Cilostazol pot entiates the inhibition of SIPA by PGE(1) and enhances its ability to increase cAMP concentrations. A single oral adminstration of 100 mg ci lostazol to healthy volunteers produced a significant inhibition of SI PA. This study demonstrates that cilostazol is an effective inhibitor of SIPA, which may be important for the prevention and the treatment o f arterial occlusive diseases. (C) 1997 Elsevier Science Inc.