Plasma angiotensin-(1-8) octapeptide measurement to assess acute angiotensin-converting enzyme inhibition with captopril administered parenterally to normal subjects.
The blood pressure (BP), heart rate (HR), and humoral effects of single intravenous (i.v.) doses of the angiotensin-converting enzyme (ACE) inhibitor captopril was investigated in five normotensive healthy volunteers. Each subject received at 1-week intervals a bolus dose of either captopril (1, 5, and 25 mg) or its vehicle. The study was conducted in a single-blind fashion, and the order of treatment phases was randomized. The different doses of captopril had no acute effect on BP and HR. They induced a dose-dependent decrease in plasma ACE activity and plasma angiotensin II levels. The angiotensin-(1-8) octapeptide was isolated by solid-phase extraction and high-performance liquid chromatography (HPLC) prior to radioimmunoassay (RIA). All three doses of captopril reduced circulating angiotensin II levels within 15 min of drug administration. Only with the 25-mg dose was the angiotensin II concentration below the detection limit at 15 min and still significantly reduced 90 min after drug administration. Simultaneous and progressive decreases in plasma aldosterone levels were observed both with ACE inhibition and during vehicle injection, but the relative fall was more pronounced after captopril administration. No adverse reaction was noticed. These results demonstrate that captopril given parenterally blocks the renin-angiotensin system in a dose-dependent manner. Only with the dose of 25 mg was the inhibition of plasma-converting enzyme activity and the reduction of plasma angiotensin II sustained for at least 1 1/2 h.
Nussberger
J
J
Division of Hypertension, Centre Hôpitalier Universitaire Vaudois, Lausanne, Switzerland.
Waeber
G
G
Waeber
B
B
Bidiville
J
J
Brunner
H R
HR
D000328:Adult; D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril