Methods: Thirty adult male Wistar Albino rats were randomly assigned to one of the following three groups: control group (n=10), dimethylsulfoxide (DMSO) group (n=10) or cilostazol (CIL) group (n=10). The rats in the control group received no treatment. In the CIL group, dissolved cilostazol in DMSO was administered at a dose of 10 mg/kg bid via i ntraperitoneal ( IP) route for six weeks. Rats in the DMSO group received an IP injection of DMSO at a volume which was similar to that used in the CIL group with cilostazol bid for the same time period. At the end of six-week treatment, acethylcholine (ACh)-induced (endothelium dependent) relaxation responses of isolated rat aortic rings in organ bath were evaluated.

Results: There was no statistically significant difference in the percent of relaxation in aortic rings between the control and DMSO groups. In the CIL group, relaxation responses to ACh concentrations of 3x10-9 Moles and higher were significantly higher, compared to the other two groups (p<0.05). Cilostazol treatment was observed to result in a response which led to a reduction of vascular tone beyond the basal tonus. This phenomenon became more evident in higher concentrations of ACh, representing a concentration-dependent augmentation of vasodilation in CIL group.

Conclusion: In this study, the sensitivity of endothelium to AChinduced vasodilatation increased in the rats receiving cilostazol treatment. We suggest that induction nitric oxide (NO) and prostacyclin (PG12) release by cilostazol may be the possible mechanisms of enhanced relaxation response of intact endothelium.