Nielsen C K, Arrigoni-Martelli E
Acta Pharmacol Toxicol (Copenh). 1981 Nov;49(5):427-31. doi: 10.1111/j.1600-0773.1981.tb00927.x.
Ring preparations of rabbit aorta were contracted by potassium (127 mM). Pinacidil (P 1134), a new vasodilator ( 2.3 x 10(-5) M), the calcium antagonists verapamil (3.4 x 10(-7) M), nifedipine (3.4 x 10(-9) M) and hydralazine (1.9 x 10(-4) M) relaxed the preparation by 50%. 50% relaxation of noradrenaline-contracted tissues was obtained with pinacidil, 6.8 x 10(-5) M, verapamil, 2.4 x 10(-3) M. At 2 x 10(-7) M concentration nifedipine was almost inactive. In ring preparations of rabbit aorta exposed to calcium-free medium and then depolarized with potassium (127 mM), pinacidil, 5 x 10(-5) M and nifedipine, 10(-8) M significantly inhibited the contractions by cumulative addition of calcium. Hydralazine, 10(-3) M had no effect. Noradrenaline-induced contractions in calcium-free medium or in presence of increasing amounts of calcium were significantly inhibited by nifedipine, 10(-8) M and hydralazine, 10(-3) M. Pinacidil, 10(-4) M had no effect. Pinacidil, 1.3 x 10(-5) M and verapamil, 2.0 x 10(-5) M inhibited by 50% the serotonin-induced increase of perfusion pressure of isolated rabbit ear artery. The noradrenaline effect in this preparation were 50% inhibited by pinacidil, 2.4 x 10(-4) M and by verapamil, 8.8 x 10(-5) M. Hydralazine, 10(-3) M exerted minor inhibitory effect. It is suggested that interference with calcium influx contributes to the vasodilator activity of pinacidil.
兔主动脉环标本在加入127 mM钾后收缩。新型血管扩张剂匹那地尔（P 1134，2.3×10⁻⁵ M）、钙拮抗剂维拉帕米（3.4×10⁻⁷ M）、硝苯地平（3.4×10⁻⁹ M）和肼屈嗪（1.9×10⁻⁴ M）可使标本松弛50%。匹那地尔（6.8×10⁻⁵ M）、维拉帕米（2.4×10⁻³ M）可使去甲肾上腺素收缩的组织松弛50%。在2×10⁻⁷ M浓度时，硝苯地平几乎无活性。在暴露于无钙培养基后再用钾（127 mM）去极化的兔主动脉环标本中，5×10⁻⁵ M的匹那地尔和10⁻⁸ M的硝苯地平通过累积添加钙可显著抑制收缩。10⁻³ M的肼屈嗪无作用。在无钙培养基中或存在逐渐增加量钙的情况下，10⁻⁸ M的硝苯地平和10⁻³ M的肼屈嗪可显著抑制去甲肾上腺素诱导的收缩。10⁻⁴ M的匹那地尔无作用。1.3×10⁻⁵ M的匹那地尔和2.0×10⁻⁵ M的维拉帕米可使50%的5-羟色胺诱导的离体兔耳动脉灌注压升高受到抑制。在该标本中，2.4×10⁻⁴ M的匹那地尔和8.8×10⁻⁵ M的维拉帕米可使去甲肾上腺素的作用受到50%的抑制。10⁻³ M的肼屈嗪产生轻微抑制作用。提示对钙内流的干扰有助于匹那地尔的血管扩张活性。
