The effect of cilostazol over endothelium dependent vasodilatation

Aim: Cilostazol is an agent bearing antiaggregant and antithrombotic properties acting via cAMP increment through inhibition of phosfodiesterase 3A. Cilostazol treatment results in an increase in cladication free walking distance (%67) and maximum walking distance (%50) in peripheral arterial disease. The aim of this study is to investigate the effect of cilostazol over vascular reactivity. In this study we extracted the thoracic aorta of the rats which were given intraperitoneal cilostazol and examined the endothelium dependent vasodilatation in organ bath.Material and Methots: 36 male Wistar Albino rats were included in the study. Thoracic aorta of the rats examined in organ bath. Rats were randomized into three groups. Group 1: Control group (n=10) no medication was applied. Group 2: DMSO group (n=10) (cilostazol was dissoluved in DMSO). Group 3: Cilostazol+DMSO group (n=16), intraperitoneal cilostazol+DMSO 10 mg/kg was given twice a day (12 hours between each dosage) to 6 weeks. Than rats were decapitated and thracic aorta were extracted. Aortic rings each 3-4 mm length were prepared by paying meticulous care for not touching to the intimal surface. Aotic rings were immersed tissue bath (20 ml) containing Krebs solution (37?C, %95 O2, %5 CO2, pH 7,4). Vasoconstriction in aortic rings were induced by means of treating them with 0,1 ml (10-4 molar) norepinephirine solution and then dose-response to acethylcholine induced endothelium dependent vasodilatation (vasorelaxation via cGMP) was studied (11 dosage as a whole).Findings: The percent of relaxation for each relaxation response at any dosage of molar acethylcholine concentration (total 11 dosage) in cilostazol group was significantly different (p<0,05) as compared with control group. The percentage of vasodilatation in vascular ring after the first 3 acethylcholine dosage was beyond the basal vascular tonus. However, there was no significant difference between control and DMSO groups.Results: Cilostazol causes vasodilatation by increasing the levels of cAMP. Cilostazol also leads to increased levels of endothelium derived PGI2-Prostacyline (vasodilatation ang antiaggregan activty). PGI2 and NO witch secreted from endothelium play important role in endothelium derived vasodilatation. Acethylcholine is known to produce vasodilatation by relaxation of vascular smotth muscle cells through inducing NO and PGI2 secretion from endothelial cells. In this study we observed that cilostazole increases the sensitivity of endothelium to vasodilator agents. This effect of cilostazol may occur either directly through increase of cAMP levels or via triggering the basal secretion of endothelium derived vasodilators (NO and PGI2). Further studies are needed for understanding the exact mechanism of cilostazol.Key words: Cilostazol, peripheral arterial disease, vasodilatation, prostacycline.Correspondence address: Nail SİREK. MD.ADÜ Faculty of Medicine Department of Cardiovascular Surgery, AYDIN