Smits J F, Struyker-Boudier H A
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Fundam Clin Pharmacol. 1991;5(8):651-61. doi: 10.1111/j.1472-8206.1991.tb00755.x.
Rilmenidine is an oxazoline analogue that has antihypertensive properties that resemble those of clonidine. Since rilmenidine has recently been described to have a relatively greater affinity for imidazoline receptors than clonidine, it was of interest to study whether this has functional consequences with regard to the regional hemodynamic responses. We investigated regional hemodynamics in conscious spontaneously hypertensive rats, equipped with miniature Doppler flow probes on the renal and mesenteric arteries and on the abdominal aorta. Clonidine (3-30 micrograms/kg) and rilmenidine (0.2-3 mg/kg) induced similar, dose-dependent reductions in heart rate. Both also induced an early hypertensive response, which was greater with rilmenidine, and similar later blood pressure reductions, which were maintained over 3 h. The early hypertensive response was associated with generalized vasoconstriction. Rilmenidine caused slightly greater mesenteric and hindquarter constriction than clonidine, whereas renal effects did not differ significantly. During the hypotensive phase, rilmenidine was a less potent mesenteric and hindquarter vasodilator than clonidine. During this phase, renal blood flow was at control levels, probably indicating autoregulation of renal flow. The minor differences in regional hemodynamic effects suggest that clonidine and rilmenidine can both be used as potent antihypertensives. The fact that rilmenidine has been suggested to possess less sedative side-effects suggests that, on this basis, it may be superior for antihypertensive drug therapy.
利美尼定是一种恶唑啉类似物，具有与可乐定相似的抗高血压特性。由于最近有人描述利美尼定对咪唑啉受体的亲和力比对可乐定相对更高，因此研究这是否会对局部血流动力学反应产生功能影响很有意义。我们在清醒的自发性高血压大鼠身上进行了局部血流动力学研究，这些大鼠的肾动脉、肠系膜动脉和腹主动脉上均安装了微型多普勒血流探头。可乐定（3 - 30微克/千克）和利美尼定（0.2 - 3毫克/千克）均可引起相似的、剂量依赖性的心率降低。两者还均可引起早期高血压反应，利美尼定引起的反应更强，后期血压降低相似，且这种降低持续3小时。早期高血压反应与全身血管收缩有关。利美尼定引起的肠系膜和后肢血管收缩比可乐定略强，而对肾脏的影响无显著差异。在降压阶段，利美尼定作为肠系膜和后肢血管舒张剂的效力比可乐定弱。在此阶段，肾血流量处于对照水平，这可能表明肾血流存在自身调节。局部血流动力学效应的微小差异表明，可乐定和利美尼定均可作为有效的抗高血压药物使用。有人认为利美尼定的镇静副作用较少，基于此，它可能在抗高血压药物治疗方面更具优势。
