Angiotensin converting enzyme inhibition: discrepancy between antihypertensive effect and suppression of enzyme activity.
With chronic angiotensin converting enzyme (ACE) inhibition, blood pressure remains controlled throughout the day despite intermittent recovery of normal function of the renin-angiotensin system. This has been taken as evidence to suggest that the disappearance of angiotensin II (Ang II) from the circulation is not the main mechanism involved in the blood pressure-lowering action of ACE inhibitors. However, the degree of ACE inhibition is often not reliably estimated by the commonly used measurements of plasma ACE activity in vitro or plasma immunoreactive Ang II levels. The most appropriate method to assess ACE activity seems to be the measurement of the ratio between circulating angiotensin-(1-8)octapeptide and angiotensin I (Ang I) concentrations. The octapeptide and angiotensin I (Ang I) concentrations. The octapeptide Ang II can be measured precisely using high pressure liquid chromatography followed by a radioimmunoassay. Even using such improved methods, with long-term ACE inhibition, there exists a clear dissociation between the time course of ACE inhibition and that of the antihypertensive effect. Although it is attractive to speculate on this basis that other pathways such as blockade of tissue renin or enhanced vasodilator activity are responsible for the antihypertensive effect of ACE inhibitors, it is important to remember that the dissociation between the pharmacokinetic profile and the time course of the antihypertensive effect is not specific for ACE inhibitors and is well known with other agents. Since intermittent reduction of circulating Ang II is still an omnipresent feature of ACE inhibition, it seems at present that ACE inhibitors reduce blood pressure predominantly by this mechanism.
Waeber
B
B
Division of Hypertension, University Hospital, Lausanne, Switzerland.
Nussberger
J
J
Juillerat
L
L
Brunner
H R
HR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000809:Angiotensins / Q000097:blood; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D000959:Antihypertensive Agents; D007703:Peptidyl-Dipeptidase A