Xiang J Z, Linz W, Becker H, Ganten D, Lang R E, Schölkens B, Unger T
Eur J Pharmacol. 1985 Jul 17;113(2):215-23. doi: 10.1016/0014-2999(85)90738-1.
The role of converting enzyme (CE) in heart function was studied by assessing the inhibition of CE activity in rat heart tissue and in isolated perfused hearts from rat, guinea-pig and rabbit (Langendorff technique). Angiotensin I (ANG I) added to the perfusate reduced coronary flow (FLO) in all species, increased force of contraction (CON) in rats, decreased CON in guinea-pigs and had no effect on CON in rabbits. In contrast, bradykinin (BK) increased FLO in all species, decreased CON in rats, increased CON in guinea-pigs and had no effect on CON in rabbits. The CE inhibitors ramipril (HOE498) 1 mg/kg and enalapril (MK421) 30 mg/kg given orally 1 h prior to killing of the animals inhibited the ANG I effects and potentiated the BK effects but had no effects on the action of ANG II. The same doses of the two CE inhibitors produced up to 24 h inhibition of CE activity measured biochemically in the heart after single oral doses. Electrical sympathetic stimulation of the cardiac nerves (SNS) in isolated rabbit heart resulted in an increase of HR and CON and in an initial decrease and subsequent increase of FLO. The effects of SNS on HR and FLO were significantly reduced following HOE498 (1 mg/kg) pretreatment. The results suggest that local CE is involved in the regulation of peptide effects in the heart, including the ANG II-mediated facilitation of neurotransmission.
通过评估大鼠心脏组织以及大鼠、豚鼠和兔离体灌流心脏（Langendorff技术）中转化酶（CE）活性的抑制情况，研究了转化酶在心脏功能中的作用。向灌流液中添加血管紧张素I（ANG I）会降低所有物种的冠状动脉血流量（FLO），增加大鼠的收缩力（CON），降低豚鼠的CON，而对兔的CON无影响。相反，缓激肽（BK）会增加所有物种的FLO，降低大鼠的CON，增加豚鼠的CON，对兔的CON无影响。在处死动物前1小时口服给予CE抑制剂雷米普利（HOE498）1 mg/kg和依那普利（MK421）30 mg/kg可抑制ANG I的作用并增强BK的作用，但对ANG II的作用无影响。单次口服这两种CE抑制剂的相同剂量后，在心脏中通过生化方法测定的CE活性抑制作用可持续长达24小时。对离体兔心脏的心脏神经进行电交感神经刺激（SNS）会导致心率（HR）和CON增加，以及FLO先降低后增加。HOE498（1 mg/kg）预处理后，SNS对HR和FLO的作用显著降低。结果表明，局部CE参与心脏中肽类作用的调节，包括ANG II介导的神经传递促进作用。
