Differential cardiovascular effects of calcium channel blocking agents: potential mechanisms.
Differential cardiovascular effects of calcium channel blocking agents: potential mechanisms.
复制标题
钙通道阻滞剂对心血管的不同影响：潜在机制。
DOI：
10.1016/s0002-9149(82)80002-7
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Schwartz,A
中科院分区：
文献类型：
--
作者：
Millard,RW;Lathrop,DA;Grupp,G;Ashraf,M;Grupp,IL;Schwartz,A
三种主要的钙通道阻滞剂，地尔硫卓、硝苯地平和维拉帕米，抑制钙进入兴奋细胞。尽管在细胞膜上有这种明显的共同作用，但当以等效血管扩张剂剂量进行评价时，这些药物在心血管变量（例如，心率、房室[A-V]传导和心肌变力状态）方面产生定量和经常定性的差异。所有三种药物均以剂量依赖性方式增加冠状动脉血流量（硝苯地平>地尔硫=维拉帕米），并在离体心房和心室中产生负性肌力作用，也以剂量依赖性方式（维拉帕米>硝苯地平>地尔硫）。而清醒犬的硝苯地平增加，维拉帕米减少，地尔硫对正性肌力状态影响不大。在麻醉狗和清醒狗中，根据心电图的P-R间期判断，地尔硫卓和维拉帕米减慢A-V传导，但硝苯地平不减慢A-V传导。戊巴比妥麻醉的动物心率减慢，但清醒的狗心率加快（硝苯地平>维拉帕米>地尔硫卓）。硝苯地平还通过明显的迷走神经阻滞作用显著干扰动脉压力感受器反射，而地尔硫卓和维拉帕米的作用不太明显。地尔硫卓，可能还有维拉帕米和硝苯地平，似乎可以延缓伴随缺血的心肌损伤。这些药物的作用机制和位点被推测是在细胞膜上;然而，也可能涉及细胞内位点。
The three major calcium channel blocking agents, diltiazem, nifedipine and verapamil, inhibit calcium entry into excitable cells. Despite this apparent common action at the cell membrane, these drugs produce quantitative and frequently qualitative differences in cardiovascular variables (for example, heart rate, atrioventricular [A-V] conduction and myocardial inotropic state) when evaluated at equieffective vasodilator doses. All three drugs increase coronary blood flow in a dose-dependent fashion (nifedipine > diltiazem = verapamil), and produce a negative inotropic effect in vitro in isolated atria and ventricles, also in a dose-dependent manner (verapamil > nifedipine > diltiazem). However, in conscious dogs nifedipineincreases, verapamildecreasesand diltiazem haslittle effecton the inotropic state. A-V conduction is slowed by diltiazem and verapamil but not by nifedipine in anesthetized dogs and in conscious dogs as judged from the P-R interval in the electrocardiogram. Heart rate is slowed in pentobarbital-anesthetized animals but is accelerated in conscious dogs (nifedipine > verapamil > diltiazem). Nifedipine also appears to interfere significantly with the arterial baroreceptor reflex by an apparent vagolytic action that is less evident with diltiazem and verapamil. Diltiazem, and possibly verapamil and nifedipine as well, appears to retard myocardial damage that accompanies ischemia. The mechanisms and sites of action of these drugs are presumed to be at the cell membrane; however, intracellular sites may also be involved.