Effect of Cilostazol in Alleviating Cardiovascular Complications through Regulation of Type 1 Plasminogen Activator Inhibitor and Transforming Growth Factor-β1 Overexpression in Experimental Rats

Cilostazol is a potent phosphodiesterase inhibitor; its major effects are prevention of platelet aggregation and dilation of blood vessels via an increase in tissue cAMP levels. This study examined the effect of cilostazol on serum cAMP, type 1 plasminogen activator inhibitor and transforming growth factor-β1 in relation to alleviating cardiovascular complications. This was achieved in rats through administration of L-NAME (0.1 mg/ml) for two weeks, and then followed by i.p. single dose of streptozotocin (65mg/kg). Rats were classified to three groups; normal rats, control diabetic hypertensive rats and the third group was treated with cilostazol (1.8 mg daily, orally) for six weeks. Cilostazol improved serum cAMP level and increased plasma NO concentration leading to dilation of blood vessels. In addition, cilostazol has beneficial lipoprotein-modifying effect. Cilostazol treatment confirmed the positive correlation between plasma PAI-1 activity and serum TGF-β1 which is beneficial in reducing the hazards of cardiovascular complications. Thus, cilostazol therapy provides a broad spectrum of effects in alleviating cardiovascular complications induced in experimental animals.