Endothelium-dependent relaxation by cilostazol, a phosphodiesteras III inhibitor, on rat thoracic aorta

The relaxation effect of cilostazol, a phosphodiesterase III inhibitor. on the thoracic aorta was investigated. Cilostazol induced the relaxation of t he thoracic aorta precontracted by phenylephrine in a concentration-depende nt manner. The concentration-dependent relaxation was shifted to the right in the endothelium denuded aorta compared with that of intact endothelium, suggesting that this relaxation was partly dependent on endothelium. Cilost azol-induced relaxation of thoracic aorta tone was reversed by treatment wi th N-G-nitro L-arginine (L-NNA), a competitive inhibitor of nitric oxide (N O) synthase. Cilostazol also significantly increased the NO level in the po rcine thoracic aorta. In rats treated with cilostazol, the urinary excretio n of nitrites, a stable metabolite of NO, and basal production of NO of the aortic ring were significantly greater than in those without treatment. Th ese findings indicate that cilostazol-induced vasodilation of the rat thora cic aorta was dependent on the endothelium, which released NO from aortic e ndothelial cells. (C) 2001 Elsevier Science Inc. All rights reserved.