Villamil-Hernández Ma Trinidad, Alcántara-Vázquez Oscar, Sánchez-López Araceli, Gutiérrez-Lara Erika J, Centurión David
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 México D.F., México.
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 México D.F., México.
Eur J Pharmacol. 2014 Oct 5;740:512-21. doi: 10.1016/j.ejphar.2014.06.036. Epub 2014 Jun 27.
The sympathetic nervous system that innervates the peripheral circulation is regulated by several mechanisms/receptors. It has been reported that prejunctional 5-HT1A, 5-HT1B, 5-HT1D, D2-like receptors and α2-adrenoceptors mediate the inhibition of the vasopressor sympathetic outflow in pithed rats. In addition, ergotamine, an antimigraine drug, displays affinity at the above receptors and may explain some of its adverse/therapeutic effects. Thus, the aims of this study were to investigate in pithed rats: (i) whether ergotamine produces inhibition of the vasopressor sympathetic outflow; and (ii) the major receptors involved in this effect. For this purpose, male Wistar pithed rats were pre-treated with gallamine (25 mg/kg; i.v.) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9; 0.03-3 Hz) or to receive i.v. bolus of exogenous noradrenaline (0.03-3 µg/kg). I.v. continuous infusions of ergotamine (1 and 1.8 μg/kgmin) dose-dependently inhibited the vasopressor responses to sympathetic stimulation but not those to exogenous noradrenaline. The sympatho-inhibition elicited by 1.8 μg/kg min ergotamine was (i) unaffected by saline (1 ml/kg); (ii) partially antagonised by WAY 100635 (5-HT1A; 30 μg/kg) and rauwolscine (α2-adrenoceptor; 300 μg/kg), and (iii) dose-dependently blocked by GR 127935 (5-HT1B/1D; 100 and 300 μg/kg) or raclopride (D2-like; 300 and 1000 μg/kg), The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. The above results suggest that ergotamine induces inhibition of the vasopressor sympathetic outflow by activation of prejunctional 5-HT1A, 5-HT1B/1D, α2-adrenoceptors and D2-like receptors in pithed rats.
支配外周循环的交感神经系统受多种机制/受体调控。据报道，突触前5-羟色胺1A、5-羟色胺1B、5-羟色胺1D、D2样受体及α2肾上腺素能受体介导了脊髓麻醉大鼠中血管升压交感神经传出冲动的抑制。此外，抗偏头痛药物麦角胺对上述受体具有亲和力，这或许可以解释其部分不良反应/治疗作用。因此，本研究旨在对脊髓麻醉大鼠进行研究：（i）麦角胺是否会抑制血管升压交感神经传出冲动；（ii）此效应涉及的主要受体。为此，雄性Wistar脊髓麻醉大鼠预先接受加拉明（25 mg/kg；静脉注射）和地昔帕明（50 μg/kg）处理，并准备刺激血管升压交感神经传出冲动（T7-T9；0.03-3 Hz）或静脉注射外源性去甲肾上腺素（0.03-3 μg/kg）推注。静脉持续输注麦角胺（1和1.8 μg/kg·min）剂量依赖性地抑制了对交感神经刺激的血管升压反应，但对外源性去甲肾上腺素的反应无此作用。1.8 μg/kg·min麦角胺引起的交感神经抑制作用：（i）不受生理盐水（1 ml/kg）影响；（ii）被WAY 100635（5-羟色胺1A；30 μg/kg）和育亨宾（α2肾上腺素能受体；300 μg/kg）部分拮抗，（iii）被GR 127935（5-羟色胺1B/1D；100和300 μg/kg）或雷氯必利（D2样；300和1000 μg/kg）剂量依赖性阻断，上述拮抗剂剂量本身不会改变交感神经诱导的血管升压反应。上述结果表明，在脊髓麻醉大鼠中，麦角胺通过激活突触前5-羟色胺1A、5-羟色胺1B/1D、α2肾上腺素能受体及D样受体诱导血管升压交感神经传出冲动的抑制。
