Tiritilli A, Levy P, Haïat R
Laboratoire de physiologie et pharmacologie cardiovasculaire, Centre hospitalier général, Saint-Gerrmainen-Laye.
Arch Mal Coeur Vaiss. 1995 Aug;88(8):1095-9.
The umbilical arteries play an important role in the foetal circulation. These vessels, which have no sympathetic tone, are a valuable model for the study of a direct pharmacological effect on vascular smooth muscle. The aims of this study were to determine if the potassium-channel reopener, nicorandil, could relax the smooth muscle of the human umbilical artery, if glibenclamide, an inhibitor of ATP-dependant potassium channels, can influence the action of nicorandil and, finally, to evaluate the role of the vascular endothelium. Rings of human umbilical artery 3 mm wide were placed in glycosated, oxygenated (95% O2, 5% CO2) Krebs-Henseleit solution, at 37 degrees C, pH 7.4 for isometric myography. The rings were contracted with 10(-5) M 5-hydroxytryptamine (5-HT). After stabilisation, a dose-effect graph of nicorandil (10(-9) to 3 x 10(-4) M) was constructed. In another series of experiments, the rings were incubated with NG nitro-L-arginine (NLA) at 10(-4) M, an inhibitor of NO-synthase, for 15 minutes and then contracted with 5-HT (10(-5) M) and relaxed with nicorandil at the same dosage. In yet another series of experiments, glibenclamide (10(-4) M) was added to the bath 15 minutes before contraction with 5-HT (10(-5) M). The vessel was then relaxed by incremental doses of nicorandil from 10(-9) to 3 x 10(-4) M. During this study, no significant difference was observed with respect to the contractions to 5-HT; moreover, the maximal relaxations obtained by nicorandil before and after glibenclamide were no significant. On the other hand, only the relaxations obtained after incubation with NLA were significant (p < 0.005). Furthermore, the pD2 did not differ significantly between the different groups of vascular rings. The authors conclude that nicorandil is a powerful dilatator of human umbilical artery. Glibenclamide has an inhibitory effect on nicorandil but only at low concentrations and in a non-competitive manner. The endothelium seems to modulate the vascular tone because relaxation is greater in the presence of an inhibitor of NO-synthase: in this type of vessel, the presence of the endothelium predisposes to the liberation of contractile factors.
脐动脉在胎儿循环中起重要作用。这些血管无交感神经张力，是研究对血管平滑肌直接药理作用的宝贵模型。本研究的目的是确定钾通道开放剂尼可地尔是否能舒张人脐动脉平滑肌，ATP依赖性钾通道抑制剂格列本脲是否能影响尼可地尔的作用，以及最后评估血管内皮的作用。将宽3毫米的人脐动脉环置于含葡萄糖、充氧（95% O₂，5% CO₂）的Krebs-Henseleit溶液中，于37℃、pH 7.4条件下进行等长肌动描记。用10⁻⁵ M 5-羟色胺（5-HT）使血管环收缩。稳定后，绘制尼可地尔（10⁻⁹至3×10⁻⁴ M）的剂量-效应图。在另一系列实验中，血管环与10⁻⁴ M的NO合酶抑制剂NG-硝基-L-精氨酸（NLA）孵育15分钟，然后用5-HT（10⁻⁵ M）收缩，再用相同剂量的尼可地尔舒张。在又一系列实验中，在与5-HT（10⁻⁵ M）收缩前15分钟，向浴槽中加入格列本脲（10⁻⁴ M）。然后用递增剂量的尼可地尔（10⁻⁹至3×10⁻⁴ M）使血管舒张。在本研究中，观察到对5-HT的收缩无显著差异；此外，格列本脲前后尼可地尔获得的最大舒张无显著差异。另一方面，仅在与NLA孵育后获得的舒张有显著差异（p < 0.005）。此外，不同组血管环之间的pD₂无显著差异。作者得出结论，尼可地尔是一种强大的人脐动脉扩张剂。格列本脲对尼可地尔有抑制作用，但仅在低浓度下且以非竞争性方式。内皮似乎调节血管张力，因为在存在NO合酶抑制剂时舒张更大：在这类血管中，内皮的存在易导致收缩因子的释放。
