Electropharmacological Effects of a New Dihydropyridine Analog on Isolated Guinea Pig Papillary Muscles and Purkinje Fibers
Electropharmacological Effects of a New Dihydropyridine Analog on Isolated Guinea Pig Papillary Muscles and Purkinje Fibers
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新型二氢吡啶类似物对离体豚鼠乳头肌和浦肯野纤维的电药理学作用
DOI：
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发表时间：
1986
影响因子：
3
通讯作者：
N. Sperelakis
中科院分区：
文献类型：
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作者：
P. Molyvdas;N. Sperelakis
摘要：比较了新型二氢吡啶FR-34235与二氢吡啶、硝苯地平和维拉帕米对豚鼠乳头肌和浦肯野纤维的正常快动作电位、慢动作电位和收缩的影响。FR-34235(10-6M)可在10~12min内阻断正常泰氏液灌流的乳头肌收缩。快速AP的最大上搏速度(+Vmax)和超调不受影响，但复极50%和90%的AP持续时间(APD50和APD90)缩短。FR-34235对快速AP和收缩的作用在洗脱后10min内被逆转。为确定钙拮抗剂对慢AP的作用，用升高[K]0的部分去极化方法使快Na+通道失活(约−45 mV)，并用异丙肾上腺素(10-6M)或组胺(10-5M)诱发慢AP。硝苯地平(10-7M)和维拉帕米(2×10-6M)可完全阻断慢动作电位。FR-34235以频率依赖性方式抑制(3×10~(-8)M)和阻断(10~(-7)M)慢的AP。这种作用可被升高的[Ca]0或药物冲刷所逆转。伴随慢AP的收缩被抑制和阻断，与+Vmax的降低平行。FR-34235对豚鼠浦肯野纤维的快速AP参数无明显影响，但对自律性有明显的抑制作用。FR-34235还以频率依赖的方式阻断浦肯野纤维的慢AP；所有药物作用在洗脱后10分钟内被逆转。结果表明，FR-34235可阻断豚鼠乳头肌和浦肯野纤维的钙离子慢通道。除了负性变力作用外，该药还有很强的负性变时性作用。这种二氢吡啶类药物的作用具有显著的频率依赖性成分。
Summary: The effects of a new dihydropyridine, FR-34235, were compared with those of the dihydropyridine, nifedipine, and verapamil on the normal fast action potentials (APs), slow APs, and contractions of guinea pig papillary muscles and Purkinje fibers. FR-34235 (10-6 M) blocked the contractions of papillary muscles superfused with normal Tyrode solution within 10–12 min. Maximal upstroke velocity (+Vmax) and overshoot of the fast APs were not affected, whereas the AP durations at 50 and 90% repolarization (APD50 and APD90) were shortened. The effects of FR-34235 on the fast APs and contractions were reversed within 10 min on washout. To determine the effects of the calcium antagonists on slow APs, the fast Na+ channels were inactivated by partial depolarization (to approximately −45 mV) by elevated [K]0, and isoproterenol (10-6 M) or histamine (10-5 M) was used to induce slow APs on stimulation. Nifedipine (10-7 M) and verapamil (2 x 10-6 M) completely blocked the slow APs. FR-34235 depressed (3 x 10-8 M) and blocked (10-7 M) the slow APs in a frequency-dependent manner. The effects were reversed by elevated [Ca]0 or washout of the drug. The contractions accompanying the slow APs were depressed and blocked in parallel with the depression of + Vmax. In guinea pig Purkinje fibers, FR-34235 had no significant effect on the fast AP parameters but produced a marked depression of automaticity. FR-34235 also blocked the slow APs of the Purkinje fibers in a frequency-dependent manner; all drug effects were reversed within 10 min on washout. The results indicate that FR-34235 blocks the Ca2+ slow channels of guinea pig papillary muscles and Purkinje fibers. In addition to its negative inotropic effect the drug has a potent negative chronotropic effect. This dihydropridine drug has a significant frequency-dependent component to its action.