Background

To investigate the effects of dipyridamole, a drug with phosphodiesterase-, adenosine reuptake-inhibiting, and prostacyclin-stimulating activity on the biological actions of nitric oxide, 30 norepinephrine-precontracted subcutaneous arterioles were prepared from specimens removed during surgery.

Methods and Results

Specimens were mounted on a myograph and relaxed through either acetylcholine, a muscarinic agonist that stimulates endothelial nitric oxide production, or sodium nitroprusside, an endothelium-independent vasodilator. Studies were performed under control conditions and after dipyridamole which potentiated in a concentration-dependent manner the vasorelaxation induced both by acetylcholine and sodium nitroprusside, indicating an endothelium-independent mechanism of action. The contribution of nitric oxide to the relaxation produced by acetylcholine was confirmed by N-monomethyl-L-arginine, a nitric oxide synthase inhibitor. In contrast, indomethacin, a cyclo-oxygenase inhibitor, was ineffective, indicating that prostacyclin stimulation could not explain the effect of dipyridamole. CGS 21680 C, an A₂-selective adenosine receptor agonist insensitive to tissue deaminase, did not influence the relaxations induced by acetylcholine, suggesting that interference with adenosine metabolism was not implicated in the potentiating action of dipyridamole.

Conclusion

Dipyridamole potentiated the vasorelaxing effect of acetylcholine and sodium nitroprusside in human subcutaneous arterioles; neither prostacyclin stimulation nor A₂ adenosine receptor stimulation could explain this effect. The data are consistent with an increase in intracellular cyclic 3’ 5'-guanosine monophosphate levels secondary to the phosphodiesterase-inhibiting properties of the drug.

中文翻译：

---

双嘧达莫在孤立的人类小动脉中增强内皮依赖性和非依赖性血管运动。

背景

为了研究具有磷酸二酯酶，腺苷再摄取抑制和前列环素刺激活性的药物双嘧达莫对一氧化氮的生物学作用的影响，从手术过程中取出的标本中制备了30个去甲肾上腺素预收缩的皮下小动脉。

方法与结果

将标本固定在肌动描记器上，并通过乙酰胆碱（一种刺激内皮一氧化氮产生的毒蕈碱激动剂）或硝普钠（一种非内皮依赖性血管扩张剂）放松。在对照条件下进行研究，并在嘧啶胺以浓度依赖性方式增强乙酰胆碱和硝普钠两者诱导的血管舒张后，表明内皮依赖性作用机制。一氧化氮合酶抑制剂N-单甲基-L-精氨酸证实了一氧化氮对乙酰胆碱产生的松弛的贡献。相反，吲哚美辛（一种环加氧酶抑制剂）无效，这表明前列环素的刺激不能解释双嘧达莫的作用。CGS 21680 C，A ₂对组织脱氨酶不敏感的选择性腺苷受体激动剂，不影响乙酰胆碱引起的松弛，这表明对双嘧达莫的增强作用不涉及对腺苷代谢的干扰。

结论

双嘧达莫可增强乙酰胆碱和硝普钠对人皮下小动脉的血管舒张作用；前列环素刺激和A ₂腺苷受体刺激均不能解释这种作用。该数据与继药物的磷酸二酯酶抑制性质之后的细胞内环状3'5'-鸟苷单磷酸水平的增加是一致的。