Dominiak P, Blöchl A
Department of Pharmacology, Medical University of Lübeck, FRG.
Basic Res Cardiol. 1991;86 Suppl 3:149-56. doi: 10.1007/978-3-662-30769-4_14.
In previous studies concerning the sympathetic outflow during converting enzyme inhibition, no significant changes after chronic treatment could be observed. Therefore, we investigated the effects of the long-acting converting enzyme inhibitor ramipril on the neuronal and extraneuronal uptake of SHR. Ramipril was administered either i.v. or orally to SHR, whereas desipramine or corticosterone were additionally infused to block the neuronal or extraneuronal uptake of catecholamines. As an index of sympathetic outflow, plasma noradrenaline and adrenaline concentrations were determined during preganglionic stimulation of the spinal cord using HPLC and ELCD. Blood pressure of SHR was measured in a carotid artery and was significantly decreased in the ramipril treated group under resting and stimulating conditions. Ramipril did not influence stimulated sympathetic outflow. However, in acute and chronic experiments ramipril led to an additive effect to desipramine concerning stimulated circulating catecholamines. Similar results could be obtained after blocking the uptake-2 with corticosterone. 3H-NA-uptake into the hearts of SHR was significantly diminished by about 10% after chronic ramipril administration. It is suggested that ramipril is able to decrease the neuronal and extraneuronal uptake of catecholamines by an unspecific effect due to the comparably high lipophilicity. The blood pressure lowering effect of ramipril is not supported by an inhibition of presynaptic noradrenaline release.
在先前有关血管紧张素转换酶抑制期间交感神经输出的研究中，未观察到慢性治疗后有显著变化。因此，我们研究了长效血管紧张素转换酶抑制剂雷米普利对自发性高血压大鼠（SHR）神经元和神经元外摄取的影响。雷米普利通过静脉注射或口服给予SHR，同时额外输注地昔帕明或皮质酮以阻断儿茶酚胺的神经元或神经元外摄取。作为交感神经输出的指标，在使用高效液相色谱法（HPLC）和电解电导检测器（ELCD）对脊髓进行节前刺激期间测定血浆去甲肾上腺素和肾上腺素浓度。在颈动脉测量SHR的血压，雷米普利治疗组在静息和刺激条件下血压均显著降低。雷米普利不影响刺激的交感神经输出。然而，在急性和慢性实验中，雷米普利对刺激的循环儿茶酚胺与地昔帕明产生相加作用。在用皮质酮阻断摄取-2后可获得类似结果。慢性给予雷米普利后，SHR心脏对3H-去甲肾上腺素的摄取显著减少约10%。提示雷米普利由于其相对较高的亲脂性，能够通过非特异性作用降低儿茶酚胺的神经元和神经元外摄取。雷米普利的降压作用并非由抑制突触前去甲肾上腺素释放所介导。
