地尔硫䓬诱导犬基底动脉平滑肌细胞的血管舒张。
Diltiazem-induced vasodilatation of smooth muscle cells of the canine basilar artery.
作者信息
Fujiwara S, Ito Y, Itoh T, Kuriyama H, Suzuki H
出版信息
Br J Pharmacol. 1982 Mar;75(3):455-67. doi: 10.1111/j.1476-5381.1982.tb09162.x.
1 The effects of diltiazem on smooth muscle cells of the canine basilar artery were investigated by means of microelectrode, double sucrose gap and isometric tension recording methods. 2 The mean membrane potential of the smooth muscle cells was -49.8 mV and they were electrically quiescent. Diltiazem (over 10(-5) M) depolarized the membrane. After pretreatment with 5 and 10 mM tetraethylammonium (TEA), an outward current pulse (1 and 2 s in duration) produced a spike and this spike was abolished by application of 10(-5) M diltiazem. 3 The spike could also be generated by the excitatory junction potential (e.j.p.) evoked by perivascular nerve stimulation (0.05 ms in pulse duration) in the presence of 5 mM TEA. Diltiazem (greater than 10(-6) M) suppressed both the spike and the e.j.ps, the suppression being more apparent for spike generation. The amplitude of the e.j.ps was reduced by diltiazem in concentrations greater than 10(-6) M. The effects were dose-dependent: when the amplitude of e.j.ps was reduced by application of diltiazem, the resulting mechanical response was also proportionally smaller. 4 The contractions evoked by 128 mM [K]o, 10(-3) M adenosine 5'-triphosphate (ATP) or, NaCl-free solution were abolished in Ca-free solutions containing 2 mM EGTA, but the amplitude of caffeine-induced contraction (10 mM) was only slightly reduced. Diltiazem, in concentrations above 3 X 10(-7) M suppressed the contraction evoked by excess [K]o, ATP or caffeine, but the inhibitory action of diltiazem on the K-induced contraction was greatest. 5 Following pretreatment with 2.5 mM [Ca]o, a contraction was evoked by caffeine in Ca-free solution. The amplitude of the caffeine-induced contraction was increased by simultaneous application of 2.5 mM [Ca]o with 128 mM [K]o and to a lesser extent by simultaneous application of 2.5 mM [Ca]o with 5.9 mM [K]o. The amplitude of the caffeine-induced contraction generated in the presence of 5.9 mM or 128 mM [K]o was suppressed to the same extent by application of diltiazem [10(-5) M) during preincubation in [Ca]o. This result suggests that the Ca stored in cell is replenished by Ca-influx from [Ca]o during the resting and active states of the membrane, and that diltiazem has no effect on the mobilization of Ca stored in the cell. 6 Thus, diltiazem acts on the canine basilar artery suppressing the Ca-influx during the active condition as a Ca-spike suppressor and the voltage-dependent Ca-influx induced by excess [K]o or by chemical depolarization. Diltiazem has no effect on the Ca mobilization from the store site. This agent also suppresses the amplitude of e.j.ps due to inhibition of the release of chemical transmitter from nerve terminals following the suppression of the Ca-influx. Diltiazem appears to act as a vasodilator on the canine basilar artery.
- 采用微电极、双蔗糖间隙和等长张力记录方法，研究了地尔硫䓬对犬基底动脉平滑肌细胞的作用。2. 平滑肌细胞的平均膜电位为-49.8 mV，且电活动静止。地尔硫䓬（超过10⁻⁵ M）使膜去极化。用5和10 mM四乙铵（TEA）预处理后，一个外向电流脉冲（持续1和2 s）产生一个峰电位，而施加10⁻⁵ M地尔硫䓬可消除该峰电位。3. 在5 mM TEA存在下，血管周围神经刺激（脉冲持续时间0.05 ms）诱发的兴奋性接头电位（e.j.p.）也可产生峰电位。地尔硫䓬（大于10⁻⁶ M）抑制峰电位和e.j.p.，对峰电位产生的抑制更明显。浓度大于10⁻⁶ M的地尔硫䓬可降低e.j.p.的幅度。这些作用呈剂量依赖性：当地尔硫䓬降低e.j.p.幅度时，所产生的机械反应也相应减小。4. 在含2 mM乙二醇双四乙酸（EGTA）的无钙溶液中，128 mM [K⁺]ₒ、10⁻³ M腺苷5'-三磷酸（ATP）或无NaCl溶液所诱发的收缩被消除，但10 mM咖啡因诱发的收缩幅度仅略有降低。浓度高于3×10⁻⁷ M的地尔硫䓬抑制过量[K⁺]ₒ、ATP或咖啡因所诱发的收缩，但地尔硫䓬对钾诱发收缩的抑制作用最大。5. 用2.5 mM [Ca²⁺]ₒ预处理后，咖啡因在无钙溶液中诱发收缩。2.5 mM [Ca²⁺]ₒ与128 mM [K⁺]ₒ同时应用可增加咖啡因诱发收缩的幅度，2.5 mM [Ca²⁺]ₒ与5.9 mM [K⁺]ₒ同时应用则在较小程度上增加该幅度。在[Ca²⁺]ₒ预孵育期间施加地尔硫䓬[10⁻⁵ M]，可同等程度地抑制在5.9 mM或128 mM [K⁺]ₒ存在下产生的咖啡因诱发收缩的幅度。该结果表明，在膜的静息和活动状态下，细胞内储存的钙通过从[Ca²⁺]ₒ内流得到补充，且地尔硫䓬对细胞内储存钙的动员无影响。6. 因此，地尔硫䓬作用于犬基底动脉，作为一种钙峰抑制剂和由过量[K⁺]ₒ或化学去极化诱导的电压依赖性钙内流抑制剂，在活动状态下抑制钙内流。地尔硫䓬对储存部位的钙动员无影响。该药物还通过抑制钙内流后神经末梢化学递质的释放来抑制e.j.p.的幅度。地尔硫䓬似乎对犬基底动脉起血管扩张剂的作用。
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