Rubanyi G M, Hoeffner U, Schwartz A, Vanhoutte P M
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota.
J Pharmacol Exp Ther. 1988 Jul;246(1):60-4.
Experiments were designed to analyze potential interactions between voltage-dependent calcium channel blockers and endothelium-dependent vascular responses. Rings of canine femoral artery were suspended for isometric force recording in organ chambers and contracted with prostaglandin F2 alpha. Removal of the endothelium had no effect on relaxations induced by d-cis-diltiazem (active stereoisomer), verapamil or nimodipine. When rings with endothelium were first partially relaxed with acetylcholine or the calcium ionophore A23187 the concentration-relaxation curve to d-cis-diltiazem (but not to verapamil or nimodipine) was significantly shifted to the right. Partial relaxation of femoral arterial rings without endothelium by sodium nitroprusside had no effect on relaxations evoked by diltiazem. Pretreatment with diltiazem (10(-6) M) had no effect on endothelium-dependent relaxations to acetylcholine in femoral artery rings. D-cis-Diltiazem partially reversed the relaxation induced by acetylcholine in a bioassay system, in which a ring of canine coronary artery without endothelium was superfused by solution passing through a segment of femoral artery with endothelium. D-cis-Diltiazem relaxed the bioassay ring when infused downstream of the perfused femoral artery with, or upstream of a femoral artery without endothelium. The effect of diltiazem was stereoselective (the less active l-cis-diltiazem had no effect). Verapamil did not reverse the relaxation induced by acetylcholine and did not affect the reversal induced by diltiazem. These findings indicate that diltiazem specifically antagonizes the production and/or the release of endothelium-derived relaxing factor(s) stimulated by acetylcholine or A23187 in canine femoral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
实验旨在分析电压依赖性钙通道阻滞剂与内皮依赖性血管反应之间的潜在相互作用。将犬股动脉环悬挂于器官浴槽中进行等长张力记录，并用前列腺素F2α使其收缩。去除内皮对d-顺式地尔硫䓬（活性立体异构体）、维拉帕米或尼莫地平诱导的舒张无影响。当内皮完整的血管环先用乙酰胆碱或钙离子载体A23187部分舒张后，d-顺式地尔硫䓬（而非维拉帕米或尼莫地平）的浓度-舒张曲线显著右移。硝普钠使无内皮的股动脉环部分舒张，对地尔硫䓬诱发的舒张无影响。用地尔硫䓬（10⁻⁶ M）预处理对股动脉环中内皮依赖性乙酰胆碱舒张无影响。在生物测定系统中，d-顺式地尔硫䓬部分逆转了乙酰胆碱诱导的舒张，该系统中无内皮的犬冠状动脉环被流经有内皮的股动脉段的溶液灌注。当在灌注的股动脉下游或无内皮的股动脉上游注入d-顺式地尔硫䓬时，其可使生物测定环舒张。地尔硫䓬的作用具有立体选择性（活性较低的l-顺式地尔硫䓬无作用）。维拉帕米不能逆转乙酰胆碱诱导的舒张，也不影响地尔硫䓬的逆转作用。这些发现表明，地尔硫䓬特异性拮抗犬股动脉中由乙酰胆碱或A23187刺激产生和/或释放的内皮源性舒张因子。（摘要截短于250字）
