ウサギ脳細動脈に対するシロスタゾールによる弛緩反応の解析

抄録

Cilostazol, an inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3), has been used clinically for the treatment of chronic arterial occlusive diseases and secondary prevention of cerebral infarction. The beneficial effect of cilostazol is attributed to both anti-platelet aggregation and vasodilation. Effects of cilostazol on resistance-sized cerebral arteries, however, have not been well elucidated. In this study, we investigated the mode of action of cilostazol on pressurized rabbit cerebral arterioles. Cerebral arterioles were cannulated and monitored with an inverted microscope. The vessels developed myogenic tone by constricting approximately 50% from the maximum passive diameter. Cilostazol (10⁻⁹–10⁻⁴ M) produced concentration-dependent vasodilation. The agent also produced a similar relaxation in the arterioles precontracted by 5-hydroxytryptamine or U46619, a stable analog of thromboxane A₂. Cilostazol (10⁻⁶ M) augmented the adenosine-induced vasodilation of the arterioles. Adenosine (10⁻⁷ M) also caused a potentiation of the cilostazol-mediated vasodilation. Nω-nitro-L-arginine methyl ester (L-NAME) (10⁻⁴ M), a nitric oxide synthase inhibitor, or aspirin (10⁻⁵ M), a cyclooxygenase inhibitor, did not significantly alter the cilostazol-induced arteriolar dilation. Furthermore, vasodilation by cilostazol was observed with endothelial-denudated arterioles. These results suggest that cilostazol produces the vasodilation of rabbit cerebral arterioles independent on the functional endothelium. [Jpn J Physiol 55 Suppl:S91 (2005)]