The Selective Inhibition of Serotonin‐ Induced Contractions of Rabbit Cerebral Vascular Smooth Muscle by Calcium‐ Antagonistic Dihydropyridines: An Investigation of the Mechanism of Action of Nimodipine
The Selective Inhibition of Serotonin‐ Induced Contractions of Rabbit Cerebral Vascular Smooth Muscle by Calcium‐ Antagonistic Dihydropyridines: An Investigation of the Mechanism of Action of Nimodipine
复制标题
钙拮抗二氢吡啶选择性抑制血清素诱导的兔脑血管平滑肌收缩：尼莫地平作用机制的研究
作者：
R. Towart
本研究通过比较钙撤除与钙拮抗剂尼莫地平[异丙基（2-甲氧基乙基）-1，4-二氢-2，6-二甲基-4-（3-硝基苯基）-3，5-吡啶二羧酸酯]的作用，研究了钙在家兔离体隐动脉和基底动脉环激活中的作用。血清素诱导的收缩的两个血管迅速抑制孵育在无钙溶液中，显示收缩的两个血管依赖于细胞外钙。尼莫地平可明显抑制钾诱导的两条血管的收缩（基底动脉：ID_（50）= 1.7 × 10 ~（10）mol/L;隐动脉：ID_（50）= 2.6 × 10 ~（10）mol/L），表明去极化诱导的钙内流（可能通过“电位敏感通道”，PSC）对尼莫地平敏感。在基底动脉中，尼莫地平可有效地抑制持续的、紧张性相的阿托宁诱导的收缩（可能通过“受体操作通道”，ROCs）（ID 50 = 7.3 × 10 - 10 mol/L）。然而，基底动脉收缩的最初短暂阶段相对不受影响（IDao = 2 × 106 mol/L），表明尼莫地平对基底动脉紧张性收缩的抑制作用不是由于5-羟色胺受体水平的拮抗作用。相反，在隐动脉中，尼莫地平在高达2.4 × 10 ~（-5）mol/L的剂量下不影响尼莫地平诱导的收缩。据推测，选择性抑制持续紧张性收缩的基底动脉是由于选择性抑制尼莫地平的钙运动通过ROCs在这个血管。激动剂诱导的外周血管中ROCs的活化似乎不受钙拮抗剂的影响。
I studied the role of calcium in the activation of isolated rings of saphenous and basilar arteries of the rabbit by comparing the effect of calcium withdrawal with the effect of the calcium antagonist nimodipine [isopropyl(2-methoxyethyl)-l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyr- idinedicarboxylate]. Serotonin-induced contractions of both vessels were inhibited quickly by incubation in calcium-free solution, showing the contractions of both vessels to be dependent on extracellular calcium. Potassium-induced contractions of both vessels were inhibited markedly by nimodipine (basilar: ID50 = 1.7 × 10∼10 mol/liter; saphenous: ID50 = 2.6 × 10∼′° mol/liter), showing depolarization- induced calcium influx (probably through “potential sensitive channels”, PSCs) to be sensitive to nimodipine. In the basilar artery the sustained, tonic phase of serotonin-induced contractions (probably through “receptor operated chennels,” ROCs) was potently inhibited (ID50 = 7.3 × 10∼10 mol/liter) by nimodipine. However, the initial short-lived phase of this contraction of the basilar artery was relatively unaffected (IDao = 2 × 106 mol/liter), indicating that the inhibitory action of nimodipine on tonic contractions of the basilar artery was not due to antagonism at the serotonin receptor level. In contrast, in the saphenous artery the serotonin-induced contractions were unaffected by nimodipine in doses up to 2.4 × 10∼5 mol/liter. It is postulated that the selective inhibition of the sustained tonic contraction of the basilar artery is due to a selective inhibition by nimodipine of calcium movement through ROCs in this vessel. Agonist-induced activation of ROCs in peripheral blood vessels does not seem to be affected by calcium antagonists.