Scarborough N L, Carrier G O
J Pharmacol Exp Ther. 1984 Dec;231(3):597-602.
The ability of nifedipine to inhibit contractions induced by non-selective and selective alpha adrenoceptor agonists and by KCl depolarization was studied in the rat aorta. The presence of alpha-2 adrenoceptors which mediate vasoconstriction was demonstrated. Furthermore, this response was highly dependent on extracellular calcium. Alpha-1 adrenoceptors were also present, but this response was dependent primarily upon intracellular calcium stores. Contractions induced by maximally effective concentrations of agonists were separated into fast and slow components of the response. Nifedipine effectively inhibited the slow component of contractions induced by norepinephrine, phenylephrine and clonidine. The slow component of the response induced by these agonists is therefore due to influx of extracellular calcium. The fast component was resistant to nifedipine treatment and is therefore assumed to be due to release of intracellular calcium. Nifedipine was equally potent at inhibiting the slow component of both alpha-1 and alpha-2 adrenoceptor-stimulated contractions and contractions due to KCl depolarization. This suggests that the calcium influx pathways activated by these two types of stimuli 1) may be the same or 2) they have similar affinities for nifedipine or 3) there is a common site of action of nifedipine on both calcium entry pathways.
在大鼠主动脉中研究了硝苯地平抑制由非选择性和选择性α肾上腺素能受体激动剂以及氯化钾去极化诱导的收缩的能力。证实了介导血管收缩的α-2肾上腺素能受体的存在。此外，这种反应高度依赖细胞外钙。α-1肾上腺素能受体也存在，但这种反应主要依赖细胞内钙储备。由最大有效浓度激动剂诱导的收缩被分为反应的快速和慢速成分。硝苯地平有效抑制去甲肾上腺素、苯肾上腺素和可乐定诱导的收缩的慢速成分。因此，这些激动剂诱导的反应的慢速成分是由于细胞外钙的内流。快速成分对硝苯地平治疗有抗性，因此被认为是由于细胞内钙的释放。硝苯地平在抑制α-1和α-2肾上腺素能受体刺激的收缩以及氯化钾去极化引起的收缩的慢速成分方面同样有效。这表明由这两种类型刺激激活的钙内流途径1）可能相同，2）它们对硝苯地平具有相似的亲和力，或者3）硝苯地平在两种钙进入途径上有共同的作用位点。
