Edelsteinová S, Lazarová Z, Lojda Z, Czirfusz A, Drábková E
Katedra farmakodynamiky a toxikológie Farmaceutickej fakulty Univerzity Komenského, Bratislava.
Cas Lek Cesk. 1991 Nov 29;130(22-23):635-9.
Calcium ions act as intracellular messengers in numerous cellular functions and participate also in the development of the atherosclerotic process. Calcium homeostasis could be an important factor in the development of atherosclerosis. One of the drugs which interferes with calcium homeostasis are calcium channel blockers. A number of studies have investigated the possibility whether these drugs may be also useful for prevention of atherosclerosis. However, other investigators have reported that calcium channel blockers did not suppress the atherosclerotic process. In our work we assumed the direct influence of calcium channel blockers on transendothelial transport mechanisms. Therefore we decided to investigate the influence of verapamil, diltiazem and isradipine on the development of experimental atherosclerosis in rabbits. Verapamil administered twice daily, 0.125 mg per kg s. c., reduced the size of atheromatous plaques in the thoracic aorta and the level of total cholesterol and triglycerides in serum. This above effect was not present after administration of diltiazem in doses of 1.0 mg per kg and isradipine 1.25 mg per kg twice daily subcutaneously. Our conclusion is that the anti-atherosclerotic effect of calcium channel blockers is dose-dependent. It is not clear whether this effect takes place in the plasma compartment and/or in the intracellular compartment.
钙离子在众多细胞功能中充当细胞内信使,并且也参与动脉粥样硬化进程的发展。钙稳态可能是动脉粥样硬化发展过程中的一个重要因素。干扰钙稳态的药物之一是钙通道阻滞剂。许多研究探讨了这些药物是否也可用于预防动脉粥样硬化的可能性。然而,其他研究人员报告称钙通道阻滞剂并不能抑制动脉粥样硬化进程。在我们的研究中,我们假定钙通道阻滞剂对跨内皮转运机制有直接影响。因此,我们决定研究维拉帕米、地尔硫䓬和伊拉地平对兔实验性动脉粥样硬化发展的影响。每天皮下注射两次维拉帕米,剂量为每千克0.125毫克,可减小胸主动脉粥样斑块的大小以及降低血清中总胆固醇和甘油三酯的水平。每天皮下注射两次剂量为每千克1.0毫克的地尔硫䓬和每千克1.25毫克的伊拉地平后,上述效果未出现。我们的结论是,钙通道阻滞剂的抗动脉粥样硬化作用是剂量依赖性的。尚不清楚这种作用是在血浆区室和/或细胞内区室中发生。