Dominiak P, Elfrath A, Türck D
Department of Physiology, University of Munich, F.R.G.
J Cardiovasc Pharmacol. 1987;10 Suppl 7:S122-4. doi: 10.1097/00005344-198706107-00025.
It has been reported that acute administration of captopril is followed by a decrease of norepinephrine (NE) release from the sympathetic nerves. Therefore, we studied the interactions between converting enzyme (CE) blocking agents and the presynaptic sympathetic nervous system after chronic administration of various CE inhibitors. Captopril, enalapril, and ramipril were administered orally to male spontaneously hypertensive rats (SHR) for 14 days. As parameters for catecholamine biosynthesis and storage, the activity of tyrosine hydroxylase and the catecholamine content of the hearts and the adrenal medulla were measured by high performance liquid chromotography (HPLC) in treated and control SHR. As an index of sympathetic outflow, plasma NE and epinephrine (E) levels were determined during preganglionic stimulation (PS) of the spinal cord. After chronic administration, no differences between the treated and control animals could be observed, either in the biosynthesis and storage of catecholamines in the heart and adrenal medulla or in the sympathetic outflow. However, after acute infusion of ramipril, a significant decrease in NE release was obtained. The dose-response curves of blood pressure vs. PS were significant shifted to the right when CE inhibitors were administered. It is suggested that the acute effect of CE inhibition on NE and E release (decreased sympathetic outflow) is blunted after long-term treatment with CE inhibitors because of increased angiotensin I (Ang I) and probably bradykinin. Both are capable of releasing NE and E at least from the adrenal medulla, like angiotensin II (Ang II).
据报道，急性给予卡托普利后，交感神经去甲肾上腺素（NE）释放减少。因此，我们研究了在长期给予各种血管紧张素转换酶（CE）抑制剂后，CE阻断剂与突触前交感神经系统之间的相互作用。将卡托普利、依那普利和雷米普利口服给予雄性自发性高血压大鼠（SHR），持续14天。通过高效液相色谱法（HPLC）测量处理组和对照组SHR心脏和肾上腺髓质中酪氨酸羟化酶的活性以及儿茶酚胺含量，以此作为儿茶酚胺生物合成和储存的参数。作为交感神经传出的指标，在脊髓节前刺激（PS）期间测定血浆NE和肾上腺素（E）水平。长期给药后，在心脏和肾上腺髓质中儿茶酚胺的生物合成和储存以及交感神经传出方面，处理组和对照组动物之间均未观察到差异。然而，急性输注雷米普利后，NE释放显著减少。给予CE抑制剂时，血压与PS的剂量反应曲线显著右移。提示长期使用CE抑制剂治疗后，由于血管紧张素I（Ang I）可能还有缓激肽增加，CE抑制对NE和E释放（交感神经传出减少）的急性作用减弱。二者都能够至少从肾上腺髓质释放NE和E，就像血管紧张素II（Ang II）一样。
