Renin inhibitors, angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists: relationships between blood pressure responses and effects on the renin-angiotensin system.
OBJECTIVE
To compare the effects of angiotensin converting enzyme (ACE) inhibitors, renin inhibitors and angiotensin II (Ang II) antagonists.


METHODS
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.


CONCLUSIONS
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.
Schalekamp
M A
MA
Department of Internal Medicine I, University Hospital Dijkzigt, Erasmus University, Rotterdam, The Netherlands.
Derkx
F H
FH
van den Meiracker
A H
AH
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000092502:Renin Inhibitors
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000092502:Renin Inhibitors