Vayssettes-Courchay C, Ragonnet C, Cordi A A, Verbeuren T J
Division of Angiology, Servier Research Institute, 11 rue des Moulineaux, 92150, Suresnes, France.
Eur J Pharmacol. 2000 Nov 24;408(3):277-88. doi: 10.1016/s0014-2999(00)00780-9.
We aimed to develop a model to study in vivo the rabbit saphenous vein pharmacology and to investigate constrictions mediated by adrenoceptor and 5-HT receptor subtypes. We used the technique of high precision ultrasonic echo-tracking for direct measurement of saphenous vein diameters in pentobarbital anesthetized rabbits. Saphenous vein constrictions induced in rabbits by the alpha(1)-adrenoceptor agonist L-phenylephrine and the 5-HT(1B) receptor agonist sumatriptan were comparable with those induced in dogs but those induced by the 5-HT(1B) and 5-HT(7) receptor agonist 5-carboxamidotryptamine failed to appear in dogs. Dose-related constrictions of rabbit veins were obtained with L-phenylephrine and the alpha(2)-adrenoceptor agonist dexmedetomidine. Frequency-related constrictions of rabbit veins induced by nerve stimulation were partially inhibited by an alpha(1)-adrenoceptor or a postsynaptic alpha(2)-adrenoceptor antagonist (prazosin and SKF 104,078) but not affected by the pre- and post-synaptic alpha(2)-adrenoceptor antagonists BRL 44408 or rauwolscine. Constrictions of rabbit veins to sumatriptan and 5-CT were inhibited by GR 127935 and those induced by quipazine, a 5-HT(2) receptor agonist were prevented by ritanserin. The initial constrictions induced by 5-CT were followed by dilatations which were inhibited by the 5-HT(7) receptor antagonist mesulergine. These data indicate that rabbit saphenous veins, in vivo and at rest, respond to activation of 5-HT(1B) and 5-HT(2) receptors, alpha(1)- and alpha(2)-adrenoceptors and nerve stimulation; the dilator effect mediated by 5-HT(7) receptor activation was also detected. The data validate a new animal model to study superficial vein reactivity and its pharmacological sensitivity.
我们旨在开发一种模型，用于在体内研究兔隐静脉药理学，并研究由肾上腺素能受体和5-羟色胺（5-HT）受体亚型介导的收缩作用。我们采用高精度超声回声跟踪技术，直接测量戊巴比妥麻醉兔的隐静脉直径。α(1)-肾上腺素能受体激动剂L-去氧肾上腺素和5-HT(1B)受体激动剂舒马曲坦在兔体内诱导的隐静脉收缩与在犬体内诱导的相似，但5-HT(1B)和5-HT(7)受体激动剂5-羧基色胺在犬体内未能诱导出收缩。L-去氧肾上腺素和α(2)-肾上腺素能受体激动剂右美托咪定可使兔静脉产生剂量相关的收缩。神经刺激诱导的兔静脉频率相关收缩，部分被α(1)-肾上腺素能受体拮抗剂或突触后α(2)-肾上腺素能受体拮抗剂（哌唑嗪和SKF 104,078）抑制，但不受突触前和突触后α(2)-肾上腺素能受体拮抗剂BRL 44408或萝芙木碱影响。GR 127935可抑制兔静脉对舒马曲坦和5-羧基色胺的收缩，5-HT(2)受体激动剂喹哌嗪诱导的收缩可被利坦色林阻断。5-羧基色胺诱导的初始收缩后出现扩张，5-HT(7)受体拮抗剂美舒麦角可抑制这种扩张。这些数据表明，兔隐静脉在体内静息状态下，对5-HT(1B)和5-HT(2)受体、α(1)-和α(2)-肾上腺素能受体的激活以及神经刺激有反应；还检测到了由5-HT(7)受体激活介导的舒张作用。这些数据验证了一种新的动物模型，可用于研究浅表静脉反应性及其药理敏感性。
