Head G A, Burke S L, Chan C K
Neuropharmacology Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
Clin Exp Hypertens. 1997 Jul-Aug;19(5-6):591-605. doi: 10.3109/10641969709083172.
We have examined the location and contribution of imidazoline receptors (IR) in mediating the hypotensive and sympatholytic actions of first and second generation anti-hypertensive agents in rabbits. We found that the hypotension produced by rilmenidine and moxonidine given intravenously (i.v.) or into the fourth ventricle (4V) was preferentially reversed by the IR antagonists idazoxan and efaroxan (compared to a selective alpha(2)-adrenoceptor antagonist 2-methoxy-idazoxan), suggesting that IR are important in the sympatho-inhibition produced by these agents. Clonidine was not preferentially reversed by the IR antagonists suggesting an action via alpha(2)-adrenoceptors. In anaesthetised rabbits, the rostral ventrolateral medulla (RVLM) was the most potent site for rilmenidine to produce the sympatho-inhibition and modulation of sympathetic baroreflexes. alpha-Methylnoradrenaline was also sympatholytic suggesting alpha(2)-adrenoceptors are also present in this site. Microinjection of the IR and alpha(2)-adrenoceptor antagonists showed that rilmenidine activates IR in the RVLM but that alpha(2)-adrenoceptors are also activated as a consequence. These studies suggest that rilmenidine acts primarily via IR in the RVLM to reduce sympathetic tone but also imply an important association of alpha(2)-adrenoceptors and IR in the region.
我们研究了咪唑啉受体（IR）在介导第一代和第二代抗高血压药物对家兔的降压和抗交感神经作用中的位置及贡献。我们发现，静脉注射（i.v.）或注入第四脑室（4V）的利美尼定和莫索尼定所产生的低血压，优先被IR拮抗剂伊达唑胺和依酚氯铵逆转（与选择性α₂-肾上腺素能受体拮抗剂2-甲氧基-伊达唑胺相比），这表明IR在这些药物产生的交感神经抑制中起重要作用。可乐定未被IR拮抗剂优先逆转，提示其通过α₂-肾上腺素能受体发挥作用。在麻醉的家兔中，延髓头端腹外侧区（RVLM）是利美尼定产生交感神经抑制和调节交感压力反射最有效的部位。α-甲基去甲肾上腺素也具有抗交感神经作用，提示该部位也存在α₂-肾上腺素能受体。IR和α₂-肾上腺素能受体拮抗剂的微量注射显示，利美尼定激活RVLM中的IR，但α₂-肾上腺素能受体也因此被激活。这些研究表明，利美尼定主要通过RVLM中的IR发挥作用以降低交感神经张力，但也意味着该区域α₂-肾上腺素能受体与IR之间存在重要联系。
