Blauw G J, van Brummelen P, Bruning T, van Zwieten P A
Department of Nephrology, University Hospital of Leiden, The Netherlands.
J Cardiovasc Pharmacol. 1988;11 Suppl 1:S41-3.
The vascular effects of serotonin and the selective 5-HT2 antagonist ketanserin were investigated in the forearm of healthy subjects. The drugs were infused into the brachial artery in doses that did not elicit systemic hemodynamic effects (0.1-80 ng/kg/min for serotonin and 5-125 ng/kg/min for ketanserin). The interaction between serotonin and ketanserin was studied by combined infusions of serotonin with ketanserin, and the relative 5-HT2 and alpha 1-adrenoceptor blocking potencies of ketanserin were studied by simultaneous infusions of the selective alpha 1-agonist methoxamine, the indirect sympathomimetic drug tyramine, and serotonin with two doses of ketanserin. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Heart rate and intra-arterial blood pressure were recorded continuously. All doses of serotonin induced an initial transient vasodilation that was followed by a steady vasodilation for the lower doses (0.1-10 ng/kg/min) and a steady vasoconstriction for the highest dose of serotonin (p less than 0.05). Ketanserin induced a dose-dependent vasodilation, which was significant from the dose of 15 ng/kg/min (p less than 0.05). The vasodilation induced by serotonin (1 ng/kg/min) was significantly enhanced by ketanserin, whereas the vasoconstriction elicited by serotonin of 80 ng/kg/min was reversed by ketanserin (p less than 0.05). The vasoconstriction induced by methoxamine and tyramine was attenuated at a lower dose of ketanserin than the vascular response induced by serotonin. It is concluded that serotonin acts mainly as a vasodilatator in healthy subjects, whereas only at very high doses is vasoconstriction mediated by 5-HT2 receptors observed. The vasodilation induced by ketanserin is most likely due to its alpha 1-adrenoceptor blocking potencies.
在健康受试者的前臂研究了血清素和选择性5-HT2拮抗剂酮色林的血管效应。将药物以不会引起全身血流动力学效应的剂量注入肱动脉（血清素为0.1 - 80 ng/kg/min，酮色林为5 - 125 ng/kg/min）。通过血清素与酮色林联合输注研究血清素与酮色林之间的相互作用，通过选择性α1-激动剂甲氧明、间接拟交感神经药物酪胺以及血清素与两剂酮色林同时输注研究酮色林相对5-HT2和α1-肾上腺素能受体的阻断效力。通过静脉阻塞体积描记法测量前臂血流量（FBF）。连续记录心率和动脉内血压。所有剂量的血清素均引起初始短暂血管舒张，随后较低剂量（0.1 - 10 ng/kg/min）时出现稳定血管舒张，而血清素最高剂量时出现稳定血管收缩（p < 0.05）。酮色林引起剂量依赖性血管舒张，从15 ng/kg/min剂量起具有显著性（p < 0.05）。酮色林显著增强了血清素（1 ng/kg/min）诱导的血管舒张，而酮色林逆转了80 ng/kg/min血清素引起的血管收缩（p < 0.05）。与血清素诱导的血管反应相比，酮色林较低剂量时即可减弱甲氧明和酪胺诱导的血管收缩。结论是，在健康受试者中血清素主要起血管舒张剂作用，而仅在非常高的剂量下才观察到由5-HT2受体介导的血管收缩。酮色林诱导的血管舒张很可能归因于其α1-肾上腺素能受体阻断效力。
