利美尼定（S 3341）与交感-肾上腺系统：犬的肾上腺素能受体、血浆及肾上腺儿茶酚胺

Rilmenidine (S 3341) and the sympathoadrenal system: adrenoreceptors, plasma and adrenal catecholamines in dogs.

Valet P, Tran M A, Damase-Michel C, de Saint-Blanquat G, Dang Tran L, Anglade F, Koenig-Berard E, Montastruc J L

Laboratoire de Pharmacologie Médicale et Clinique, INSERM U 317, Faculté de Médecine, Toulouse, France.

J Auton Pharmacol. 1988 Dec;8(4):319-26. doi: 10.1111/j.1474-8673.1988.tb00575.x.

Abstract

The effects of rilmenidine, a new alpha 2-adrenoreceptor agonist with antihypertensive properties, were investigated on plasma catecholamines, blood cell adrenoreceptors and adrenal medullary function. 2. In conscious sino-aortic denervated (SAD) dogs, rilmenidine (1 mg kg-1 orally for 2 weeks) significantly reduced both blood pressure and heart rate when compared with placebo treatment. The drug decreased plasma noradrenaline and adrenaline levels and corrected the decrease in leucocyte beta-adrenoreceptors observed in placebo-treated SAD dogs. There was no change in platelet alpha 2-adrenoreceptors. 3. In anaesthetized normotensive dogs, rilmenidine (0.1 and 0.3 mg kg-1 i.v.) induced a dose-dependent decrease in both cardiovascular parameters (blood pressure and heart rate) and catecholamine release from the adrenal medulla. 4. The present study shows that rilmenidine decreases sympathetic tone mainly by an action on the adrenal medulla. In addition, its ability to lower blood pressure in SAD dogs, i.e. a model of hypertension in which high sympathetic tone is present, indicates that rilmenidine may also depress other parts of the sympathetic nervous system.

摘要

研究了具有抗高血压特性的新型α2 - 肾上腺素能受体激动剂利美尼定对血浆儿茶酚胺、血细胞肾上腺素能受体和肾上腺髓质功能的影响。2. 在清醒的去窦弓神经（SAD）犬中，与安慰剂治疗相比，利美尼定（1毫克/千克口服，持续2周）显著降低了血压和心率。该药物降低了血浆去甲肾上腺素和肾上腺素水平，并纠正了安慰剂治疗的SAD犬中观察到的白细胞β - 肾上腺素能受体减少。血小板α2 - 肾上腺素能受体无变化。3. 在麻醉的正常血压犬中，利美尼定（0.1和0.3毫克/千克静脉注射）导致心血管参数（血压和心率）以及肾上腺髓质儿茶酚胺释放呈剂量依赖性降低。4. 本研究表明，利美尼定主要通过作用于肾上腺髓质来降低交感神经张力。此外，其在SAD犬（即存在高交感神经张力的高血压模型）中降低血压的能力表明，利美尼定也可能抑制交感神经系统的其他部分。