Supersensitivity of atherosclerotic rabbit aorta to ergonovine. Mediation by a serotonergic mechanism.
Supersensitivity of atherosclerotic rabbit aorta to ergonovine. Mediation by a serotonergic mechanism.
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动脉粥样硬化兔主动脉对麦角新碱的超敏感性。
DOI：
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发表时间：
1980
影响因子：
15.9
通讯作者：
M. Yokoyama
中科院分区：
文献类型：
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作者：
P. D. Henry;M. Yokoyama
冠状血管痉挛患者似乎对麦角碱的冠状动脉收缩作用超敏感。为了确定动脉粥样硬化是否会改变动脉反应性并使动脉对麦角碱敏感，我们比较了对照兔和高胆固醇饲粮兔离体主动脉的收缩反应。主动脉条安装在肌图中监测等长张力，在含氧克雷布斯缓冲液中平衡，并暴露于分级浓度的激动剂和拮抗剂中。麦角碱在动脉粥样硬化动脉中的浓度-反应关系表现出明显降低的收缩阈浓度（0.5 pM vs.对照组的0.23 muM），显著降低的一半有效剂量（ED(50)）值，以及增强的最大反应。此外，动脉粥样硬化动脉中血清素的浓度-反应关系也出现了类似的变化，尽管变化不那么明显。相比之下，对34 mM KCl的反应几乎相同，两组中苯肾上腺素的浓度-反应关系相似。在对照动脉中，0.1毫微克酚妥拉明和0.1毫微克吡唑嗪对1毫微克麦角碱的反应分别抑制了71%和90%。然而，在动脉粥样硬化动脉中，相同浓度的α -受体阻滞剂对0.01 ma麦角碱的抑制作用小于10%。另一方面，0.1 μ m的赛heptadine（一种5 -羟色胺能拮抗剂）抑制了82%的这些反应。因此，对麦角碱的超敏感似乎主要是由血清素能机制介导的。这些结果表明，动脉粥样硬化动脉中的平滑肌可能对特定的血管收缩刺激超敏感，这种变化可能导致体内动脉功能障碍。
Patients with coronary vasospasm appear to be supersensitive to the coronary constrictor effects of ergonovine. To determine whether atherosclerosis alters arterial reactivity and sensitizes arteries to ergonovine, contractile responses of isolated aortae from control rabbits and from rabbits fed a high-cholesterol diet were compared. Aortic strips were mounted in a myograph for the monitoring of isometric tension, equilibrated in oxygenated Krebs buffer, and exposed to graded concentrations of agonists and antagonists. The concentration-response relation for ergonovine in atherosclerotic arteries exhibited a markedly depressed constrictor threshold concentration (0.5 pM vs. 0.23 muM in controls), a significantly lowered one-half effective dose (ED(50)) value, and an augmented maximal response. Furthermore, atherosclerotic arteries showed similar, although less pronounced changes in the concentration-response relation for serotonin. In contrast, responses to 34 mM KCl were virtually identical, and the concentration-response relation for phenylephrine were similar in the two groups. In control arteries, 0.1 muM phentolamine and 0.1 muM prazosin suppressed responses to 1 muM ergonovine by 71 and 90%, respectively. However, in atherosclerotic arteries alpha-blockers in the same concentration inhibited responses to 0.01 muM ergonovine by less than 10%. On the other hand, 0.1 muM cyproheptadine, a serotonergic antagonist, suppressed these responses by 82%. Thus, the supersensitivity to ergonovine appeared to be mediated predominantly by a serotonergic mechanism. These results indicate that smooth muscle in atherosclerotic arteries may be supersensitive to specific vasoconstricting stimuli, a change that might contribute to arterial dysfunction in vivo.