Zwaveling J, Winkler Prins E A, Pfaffendorf M, van Zwieten P A
Department of Pharmacotherapy, University of Amsterdam, Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1996 Mar;353(4):438-44. doi: 10.1007/BF00261441.
We investigated the influence of hyperthyroidism on relaxant responses of small mesenteric resistance arteries to beta-adrenoceptor agonists and to compounds stimulating the corresponding second-messenger system. Hyperthyroidism was induced by feeding rats for 28 days with 5 mg/kg L-thyroxine (T4)-containing rat chow. This treatment produced a stable hyperthyroid state, as indicated by several biochemical/metabolic and haemodynamic parameters. Preparations of small mesenteric arteries were mounted in an isometric wire myograph. Subsequently, concentration-effect curves were determined for isoproterenol, noradrenaline and salbutamol as well as for forskolin, dibutyryl-cAMP and theophylline. We also determined concentration-effect curves to the beta-adrenoceptor agonists in the presence of ICI 118,551 and CGP 20712A (i.e., in the presence of a selective beta 2- and beta 1-adrenoceptor antagonist, respectively). Apparent pA2-values were calculated to determine which beta-adrenoceptor subtype causes vasodilation. These experiments indicate that beta-adrenoceptor-mediated vasodilation involves both beta 1- and beta 2-adrenoceptors in mesenteric resistance vessels of both hyperthyroid and control rats. In our experiments hyperthyroidism has a sensitizing influence on vascular responses induced by the beta-adrenoceptor agonist isoproterenol and the selective beta 2-adrenoceptor agonist salbutamol. Sensitization to isoproterenol was abolished in the presence of ICI 118,551, whereas it was emphasized in the presence of CGP 20712A. Although this was not fully supported by the results obtained with noradrenaline, these results indicate that the sensitization to beta-adrenoceptor agonists is probably limited to the beta 2-adrenoceptor/G-protein complex and not associated with alterations of the corresponding second messenger system.
我们研究了甲状腺功能亢进对小肠系膜阻力小动脉对β-肾上腺素能受体激动剂以及对刺激相应第二信使系统的化合物的舒张反应的影响。通过给大鼠喂食含5mg/kg L-甲状腺素（T4）的大鼠饲料28天来诱导甲状腺功能亢进。如几个生化/代谢和血流动力学参数所示，这种处理产生了稳定的甲状腺功能亢进状态。将小肠系膜小动脉标本安装在等长钢丝肌动描记器中。随后，测定了异丙肾上腺素、去甲肾上腺素和沙丁胺醇以及福斯可林、二丁酰环磷腺苷和茶碱的浓度-效应曲线。我们还在ICI 118,551和CGP 20712A存在的情况下（即分别在选择性β2-和β1-肾上腺素能受体拮抗剂存在的情况下）测定了对β-肾上腺素能受体激动剂的浓度-效应曲线。计算表观pA2值以确定哪种β-肾上腺素能受体亚型引起血管舒张。这些实验表明，β-肾上腺素能受体介导的血管舒张涉及甲状腺功能亢进大鼠和对照大鼠的肠系膜阻力血管中的β1-和β2-肾上腺素能受体。在我们的实验中，甲状腺功能亢进对β-肾上腺素能受体激动剂异丙肾上腺素和选择性β2-肾上腺素能受体激动剂沙丁胺醇诱导的血管反应有敏化作用。在ICI 118,551存在的情况下，对异丙肾上腺素的敏化作用被消除，而在CGP 20712A存在的情况下则增强。尽管去甲肾上腺素的结果并未完全支持这一点，但这些结果表明，对β-肾上腺素能受体激动剂的敏化作用可能仅限于β2-肾上腺素能受体/G蛋白复合物，并且与相应第二信使系统的改变无关。
