Effects of cilostazol, a selective cyclic AMP phosphodiesterase inhibitor on isolated rabbit spinal arterioles.
Effects of cilostazol, a selective cyclic AMP phosphodiesterase inhibitor on isolated rabbit spinal arterioles.
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西洛他唑（一种选择性环 AMP 磷酸二酯酶抑制剂）对离体兔脊髓小动脉的影响。
DOI：
10.2170/jjphysiol.52.471
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
T. Ohhashi
中科院分区：
文献类型：
--
作者：
Y. Yashiro;T. Ohhashi
西洛他唑是鸟苷3‘：5’-环一磷酸(CGMP)抑制的3‘：5’-环一磷酸(CAMP)磷酸二酯酶(PDE3)的有效抑制剂，已被临床用于治疗慢性周围动脉闭塞症。西洛他唑的有益作用归因于抗血小板聚集活性和血管扩张。然而，西洛他唑对耐药大小的血管形成的影响还没有很好的文献记载。此外，血管扩张的机制和对内皮功能的影响还不完全清楚。因此，我们利用分离的加压兔脊髓小动脉，特别参照功能性内皮，研究了西洛他唑的血管扩张作用。西洛他唑、乙酰胆碱(ACh)、异卡巴环素(前列环素类似物)和硝普钠(SNP)均对具有内源性肌源性张力的脊髓小动脉产生浓度依赖性的血管扩张作用。这些激动剂的效力顺序为：水胺卡巴环素；ACh>；SNP>；西洛他唑。吲哚美辛(10微米)、N(欧米茄)-硝基-L-精氨酸甲酯(L，一氧化氮合酶抑制剂，30微米)或化学剥离内皮细胞均不能显著改变西洛他唑引起的小动脉扩张。此外，给予ACh(100 NM)刺激内皮源性松弛因子的释放，或用异卡巴环素(1 NM)或SNP(3 NM)处理，均不能显著改善西洛他唑的血管扩张作用。这些结果表明，西洛他唑对分离的加压兔脊髓小动脉具有不依赖于功能性内皮的血管扩张作用。我们推测，西洛他唑对脊髓小动脉的血管扩张作用可能归因于一种未知的机制，该机制与PDE3抑制无关。
Cilostazol, a potent inhibitor of guanosine 3':5'-cyclic monophosphate (cGMP)-inhibited adenosine 3':5'-cyclic monophosphate (cAMP) phosphodiesterase (PDE3), has been used clinically for the treatment of chronic peripheral arterial occlusive disease. The beneficial effect of cilostazol is attributed to both anti-platelet aggregating activity and vasodilation. However, the effect of cilostazol on resistance-sized vasculature is not well documented. Furthermore, mechanisms of vasodilation and influence on endothelium function are not fully understood. Thus, we investigated the vasodilator action of cilostazol using isolated, pressurized rabbit spinal arterioles with special reference to the functional endothelium. Cilostazol, acetylcholine (ACh), isocarbacyclin (prostacyclin analogue), and sodium nitroprusside (SNP) all produced concentration-dependent vasodilations of isolated spinal arterioles with endogenous myogenic tone. The order of potency of these agonists was isocarbacyclin>ACh>SNP>cilostazol. Indomethacin (10 micro M, a cyclo-oxygenase inhibitor), N(omega)-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 30 micro M), or chemical denudation of the endothelial cells did not significantly alter the cilostazol-induced arteriolar dilation. Furthermore, stimulating the release of endothelium-derived relaxing factors by administering ACh (100 nM), or treating with isocarbacyclin (1 nM) or SNP (3 nM) did not significantly modify the cilostazol-induced vasodilation. These results suggest that cilostazol produces the vasodilation of isolated, pressurized rabbit spinal arterioles independent of the functional endothelium. We infer that the vasodilator action of cilostazol in the spinal arterioles may be attributed to a yet unknown mechanism that is independent of the PDE3 inhibition.