Mechanism of coronary vasoconstriction induced by carbocyclic thromboxane A2.
Mechanism of coronary vasoconstriction induced by carbocyclic thromboxane A2.
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碳环血栓素A2诱导冠状动脉收缩的机制。
DOI：
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发表时间：
1981
影响因子：
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通讯作者：
K. C. Nicolaou
中科院分区：
文献类型：
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作者：
E. F. Smith;A. M. Lefer;K. C. Nicolaou
本实验观察了碳环血栓素A_2（CTA_2）收缩猫胸主动脉条和离体冠状动脉的机制。CTA 2是一种稳定的血栓烷类似物，在50 pg/ml或更高浓度下产生冠状动脉收缩。在恒定流量下，5 ng/ml CTA 2使灌注压增加40 +/- 4 mmHg。钙拮抗剂硝苯地平在1 ng/ml（NS）、10 ng/ml（NS）、100 ng/ml（P <0.01）和1，000 ng/ml（P <0.005）时分别使CTA 2诱导的血管收缩减少8%、22%、65%和75%。其他钙拮抗剂也显着减少CTA 2诱导的冠状动脉收缩。钙拮抗剂对血管收缩的抑制作用不是由于直接的血栓素受体拮抗作用，因为硝苯地平不能阻止CTA 2诱导的猫血管收缩，血管收缩不依赖于外部钙。将外部Ca 2+浓度降低至0.63 mM显著降低了大部分CTA 2浓度-反应范围内的冠状动脉收缩。酚妥拉明（1-50 μ g/ml）、酚苄明（1-100 μ g/ml）和saralasin（0.1-10 μ g/ml）对CTA 2诱导的冠状动脉收缩均无显著影响。结果表明，血栓素收缩冠状动脉血管的机制是通过一个特定的血栓素受体，这是依赖于向内的钙流。数据还表明，钙拮抗剂治疗冠状动脉血管痉挛的疗效可能与其非竞争性抑制血栓素诱导的血管收缩的能力有关。
The mechanism of carbocyclic thromboxane A2 (CTA2) vasoconstriction was studied in thoracic aortic strips and isolated perfused cat coronary arteries. CTA2, a stable thromboxane analog, produced coronary constriction at 50 pg/ml or greater. At constant flow, 5 ng/ml CTA2 increased perfusion pressure 40 +/- 4 mmHg. The calcium antagonist nifedipine reduced CTA2-induced vasoconstriction by 8% at 1 ng/ml (NS), 22% at 10 ng/ml (NS), 65% at 100 ng/ml (P less than 0.01), and 75% at 1,000 ng/ml (P less than 0.005). Other calcium antagonists also significantly reduced CTA2-induced coronary constriction. Inhibition of vasoconstriction by calcium antagonists was not due to direct thromboxane-receptor antagonism, inasmuch as nifedipine did not prevent CTA2-induced contraction in cat aortas, vessels that are not dependent on external calcium for contraction. Reducing external Ca2+ concentration to 0.63 mM significantly reduced coronary constriction over most of the CTA2 concentration-response range. Phentolamine (1-50 micrograms/ml), phenoxybenzamine (1-100 micrograms/ml), and saralasin (0.1-10 micrograms/ml) were all without significant effect on CTA2-induced coronary constriction. The results indicate that the mechanism of thromboxane coronary vasoconstriction is by a specific thromboxane receptor that is dependent on an inward calcium flux. The data also suggest that the efficacy of calcium antagonists in coronary vasospasm may be related to their ability to noncompetitively inhibit thromboxane-induced vasoconstriction.