Schalekamp M A, Derkx F H, van den Meiracker A H
Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
J Hypertens Suppl. 1992 Dec;10(7):S157-64.
To compare the effects of angiotensin converting enzyme (ACE) inhibitors, renin inhibitors and angiotensin II (Ang II) antagonists.
Survey of data from recent studies. DISCREPANCY BETWEEN BLOOD PRESSURE REDUCTION INDUCED BY ACE INHIBITORS AND PLASMA ANG II LEVELS: Studies on the effects of ACE inhibition in hypertensive subjects have suggested that with chronic ACE inhibitor treatment, blood pressure remains lowered even when plasma Ang II returns to normal. However, this discrepancy may be largely an artefact related to difficulties in measuring low Ang II levels in the presence of high angiotensin I (Ang I) levels. Even with modern sensitive and specific Ang II assays it can be difficult to monitor in vivo ACE inhibition (Ang II:I ratio in plasma) because of ex vivo Ang II formation. Recently, in measuring 24-h blood pressure responses to ACE inhibitor treatment, we have obtained good correlations between the time-course of the blood pressure response and the change in circulating Ang II. PROBLEMS IN MEASURING RENIN ACTIVITY: Routine assays of renin activity in plasma can lead to an overestimate of the degree of in vivo inhibition during renin inhibitor treatment, because some protease inhibitors that are used in these assays can cause an ex vivo displacement of protein-bound renin inhibitor, thereby increasing its free concentration. This must be taken into account when using the ratio of enzymatically active renin to immunoreactive renin as an index of in vivo renin inhibition. BLOOD PRESSURE RESPONSE AND ANG II LEVELS WITH RENIN INHIBITORS AND ANG II ANTAGONISTS: Results published so far seem to indicate that with these drugs, as with the ACE inhibitors, the magnitude of the blood pressure effect is correlated with the decrease in the 'effective' Ang II concentration at the receptor sites. However, the time-course of the two effects may be different; with the renin inhibitors, the maximum effect on pressure was delayed compared with the effect on Ang II.
Further studies are needed to establish the exact time-course of renin and Ang II changes and their relationship to blood pressure. Only with rigorously controlled assays will it be possible to answer the question whether, for a given change in 'effective' Ang II concentration at the receptor sites, the effect on blood pressure is different with the three classes of anti-renin-angiotensin drugs.
比较血管紧张素转换酶（ACE）抑制剂、肾素抑制剂和血管紧张素II（Ang II）拮抗剂的作用。
对近期研究数据进行综述。ACE抑制剂所致血压降低与血浆Ang II水平之间的差异：关于ACE抑制对高血压患者作用的研究表明，在长期使用ACE抑制剂治疗时，即使血浆Ang II恢复正常，血压仍保持降低。然而，这种差异很大程度上可能是一种假象，与在高血管紧张素I（Ang I）水平存在时难以测量低Ang II水平有关。即使使用现代灵敏且特异的Ang II检测方法，由于体外Ang II的形成，也可能难以监测体内ACE抑制情况（血浆中Ang II:I比值）。最近，在测量24小时血压对ACE抑制剂治疗的反应时，我们发现血压反应的时间进程与循环中Ang II的变化之间存在良好的相关性。测量肾素活性的问题：血浆中肾素活性的常规检测可能导致在肾素抑制剂治疗期间高估体内抑制程度，因为这些检测中使用的一些蛋白酶抑制剂可导致体外蛋白质结合的肾素抑制剂被置换，从而增加其游离浓度。在将酶活性肾素与免疫反应性肾素的比值用作体内肾素抑制指标时，必须考虑到这一点。肾素抑制剂和Ang II拮抗剂的血压反应及Ang II水平：迄今为止发表的结果似乎表明，使用这些药物时，与ACE抑制剂一样，血压效应的大小与受体部位“有效”Ang II浓度的降低相关。然而，这两种效应的时间进程可能不同；与肾素抑制剂相比，对血压的最大效应出现延迟。
需要进一步研究以确定肾素和Ang II变化的确切时间进程及其与血压的关系。只有通过严格控制的检测，才有可能回答对于受体部位“有效”Ang II浓度的给定变化，这三类抗肾素 - 血管紧张素药物对血压的影响是否不同这一问题。
