Johnston C I, Jackson B, Cubela R, Arnolda L
Clin Exp Hypertens A. 1984;6(1-2):551-61. doi: 10.3109/10641968409062583.
The mechanism(s) for the hypotensive effect of Angiotensin Converting Enzyme (ACE) inhibitors remains elusive. This is because of the multiplicity of the biological actions of angiotensin, the dual role of ACE and the ability of the inhibitors to induce the enzyme. After a single dose of enalapril (MK421), a new ACE inhibitor, in patients with essential hypertension a close linear relationship between the plasma level of enalaprilic acid (MK422) and the degree of ACE inhibition could be demonstrated. Furthermore the degree of ACE inhibition was linearly related to the hormonal changes and to the fall in blood pressure. After chronic administration of enalapril the plasma levels of MK422 were found to be dose dependent. As in the acute study there was also a linear relationship between the plasma level of MK422 and the degree of ACE inhibition. However, the plasma enalaprilic acid level-ACE inhibition dose response curve after chronic administration was shifted to the right, compared to the dose response curve after acute administration suggesting that ACE had been induced during chronic administration of enalapril in humans. There were direct linear relationships between both the degree of ACE inhibition the plasma and enalaprilic acid (MK422) level to the fall in mean arterial pressure. These results suggest that regardless of the final mechanism for the hypotensive action of ACE inhibitors it is a consequence of their inhibition of the enzyme.
血管紧张素转换酶（ACE）抑制剂产生降压作用的机制仍不清楚。这是因为血管紧张素具有多种生物学作用，ACE具有双重作用，且抑制剂能够诱导该酶的产生。在原发性高血压患者中单次服用新型ACE抑制剂依那普利（MK421）后，可证明依那普利酸（MK422）的血浆水平与ACE抑制程度之间存在密切的线性关系。此外，ACE抑制程度与激素变化及血压下降呈线性相关。长期服用依那普利后，发现MK422的血浆水平呈剂量依赖性。与急性研究一样，MK422的血浆水平与ACE抑制程度之间也存在线性关系。然而，与急性给药后的剂量反应曲线相比，长期给药后的血浆依那普利酸水平-ACE抑制剂量反应曲线向右移动，这表明在人类长期服用依那普利期间ACE被诱导产生。ACE抑制程度、血浆和依那普利酸（MK422）水平与平均动脉压下降之间均存在直接的线性关系。这些结果表明，无论ACE抑制剂降压作用的最终机制如何，都是其抑制该酶的结果。
