Kruse H J, Bauriedel G, Heimerl J, Höfling B, Weber P C
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Munich, Germany.
J Cardiovasc Pharmacol. 1994 Aug;24(2):328-35.
Dihydropyridine (DHP) calcium channel blockers are widely used in treatment of coronary artery disease. To evaluate the specific role of L-type calcium channels in the antianginal and possibly antiatherosclerotic properties of DHP inhibitors, we examined the effects of a 1,4-DHP agonist and antagonist on angiotensin II (ANG II)- and serum-stimulated calcium influx and proliferation of human coronary smooth muscle cells (cSMC). Fluorometry of fura-2 was used to measure changes in free cytosolic Ca2+ concentration ([Ca2+]i) in cSMC after short- and long-term pretreatment with the calcium agonist Bay K 8644 or the antagonist nitrendipine, respectively. Proliferative activity was quantified during exponential growth in serum-supplemented medium with or without both DHPs. Short- and long-term pretreatment with Bay K 8644 increased basal [Ca2+]i significantly in resting cells and augmented ANG II- and serum-induced sustained [Ca2+]i responses. Concordantly, proliferation rate was increased. In contrast, nitrendipine had no significant effect on basal or stimulated [Ca2+]i after short-term treatment, but decreased [Ca2+]i after 24-h incubation, attenuated the plateau phase of ANG II- and serum-evoked [Ca2+]i transients, and reduced proliferative activity of these cells. The results indicate that 1,4-DHPs modulate ANG II- and serum-induced Ca2+ influx in cSMC. Thus, L-type calcium channels may contribute to [Ca2+]i transients evoked by ANG II and serum. Moreover, the modulating effects of both DHPs on proliferative activity suggest involvement of DHP-sensitive calcium channels. Calcium influx through L-type channels may be one of the mechanisms that determine responsiveness to vasoconstrictors and proliferative activity of human cSMC.
二氢吡啶（DHP）钙通道阻滞剂广泛用于治疗冠状动脉疾病。为了评估L型钙通道在DHP抑制剂抗心绞痛及可能的抗动脉粥样硬化特性中的具体作用，我们研究了一种1,4 - DHP激动剂和拮抗剂对血管紧张素II（ANG II）和血清刺激的人冠状动脉平滑肌细胞（cSMC）钙内流及增殖的影响。分别用钙激动剂Bay K 8644或拮抗剂尼群地平对cSMC进行短期和长期预处理后，采用fura - 2荧光测定法测量游离胞质Ca2 +浓度（[Ca2 +]i）的变化。在添加或不添加两种DHP的血清补充培养基中，在指数生长期对增殖活性进行定量。短期和长期用Bay K 8644预处理可显著增加静息细胞的基础[Ca2 +]i，并增强ANG II和血清诱导的持续性[Ca2 +]i反应。相应地，增殖率增加。相比之下，尼群地平在短期处理后对基础或刺激的[Ca2 +]i没有显著影响，但在孵育24小时后降低了[Ca2 +]i，减弱了ANG II和血清诱发的[Ca2 +]i瞬变的平台期，并降低了这些细胞的增殖活性。结果表明，1,4 - DHPs可调节ANG II和血清诱导的cSMC钙内流。因此，L型钙通道可能参与ANG II和血清诱发的[Ca2 +]i瞬变。此外，两种DHP对增殖活性的调节作用表明DHP敏感钙通道参与其中。通过L型通道的钙内流可能是决定人cSMC对血管收缩剂反应性和增殖活性的机制之一。
