Van Nueten J M, Janssen P A, De Ridder A, Vanhoutte P M
Eur J Pharmacol. 1982 Feb 5;77(4):281-7. doi: 10.1016/0014-2999(82)90130-3.
Experiments were designed to determine whether or not ketanserin (R 41 468) antagonizes the augmentation by 5-hydroxytryptamine of contractions evoked in isolated arteries by non-adrenergic vasoconstrictor substances. Rings of rabbit femoral arteries were studied under isometric conditions in organ chambers filled with Krebs-Henseleit solution (37 degrees C). Ketanserin, unlike methysergide and LSD, was devoid of agonistic properties. It competitively antagonized contractile responses to 5-hydroxytryptamine and, at higher concentrations, to histamine. 5-Hydroxytryptamine amplified the contractions evoked by threshold concentrations of histamine, angiotensin II and prostaglandin F2 alpha; in all three cases, the amplification was antagonized by comparable concentrations of ketanserin. These experiments indicate that the interaction of 5-hydroxytryptamine with S2-receptors of the vascular smooth muscle cells is essential to allow the expression of the monoamine-induced amplification of the response to other vasoconstrictor substances. The inhibition by ketanserin of the amplifying effect of 5-hydroxytryptamine on vascular responses may help explain the antihypertensive properties of the compound.
设计实验以确定酮色林（R 41 468）是否能拮抗5-羟色胺对非肾上腺素能血管收缩物质在离体动脉中诱发的收缩的增强作用。在充满Krebs-Henseleit溶液（37℃）的器官浴槽中，在等长条件下研究兔股动脉环。与甲基麦角新碱和麦角酸二乙胺不同，酮色林没有激动活性。它竞争性拮抗对5-羟色胺的收缩反应，在较高浓度时也拮抗对组胺的收缩反应。5-羟色胺增强了阈浓度组胺、血管紧张素II和前列腺素F2α诱发的收缩；在所有这三种情况下，这种增强作用都被相当浓度的酮色林所拮抗。这些实验表明，5-羟色胺与血管平滑肌细胞的S2受体相互作用对于单胺诱导的对其他血管收缩物质反应的增强作用的表达至关重要。酮色林对5-羟色胺对血管反应的增强作用的抑制可能有助于解释该化合物的抗高血压特性。
