Value of different clinical and biochemical correlates to assess angiotensin converting enzyme inhibition.
In a double-blind study, we compared the value of different approaches to assess blockade of angiotensin (Ang) II generation in 10 normal volunteers treated with the new Ang-converting enzyme (ACE) inhibitor temocapril. Plasma concentration of the diacid active metabolite of temocapril, plasma Ang I and II levels, plasma ACE activity, and inhibition of the pressor response to repeated intravenous (i.v.) doses of Ang I were measured before and repeatedly after different doses of tempocapril or placebo. In vivo ACE activity, estimated by the plasma Ang II/Ang I ratio, correlated well with temocapril diacid concentration (r = 0.85, n = 148) and with systolic and diastolic blood pressure (SBP, DBP) responses to Ang I (r = 0.76 and r = 0.79, n = 148). SBP and DBP responses to Ang I were also strongly related to temocapril diacid concentration (r = -0.81 and r = -0.88, n = 148). ACE activity measured in vivo reliably predicts the decrease in Ang-dependent BP to be achieved by ACE inhibitors.
Delacrétaz
E
E
Division of Hypertension, University Hospital, Lausanne, Switzerland.
Nussberger
J
J
Püchler
K
K
Wood
A J
AJ
Robinson
P R
PR
Waeber
B
B
Brunner
H R
HR
D000284:Administration, Oral; D000328:Adult; D000803:Angiotensin I / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004341:Drug Evaluation; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D015203:Reproducibility of Results; D013607:Tablets; D013841:Thiazepines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D013607:Tablets; D013841:Thiazepines; D000804:Angiotensin II; C055603:temocapril hydrochloride; D000803:Angiotensin I