Investigation of the biochemical effects of renin inhibition in normal volunteers treated by an ACE inhibitor.
1. In order to investigate accurately the biochemical effects of renin inhibition in man, we have developed a sensitive assay to measure angiotensin I (1-10) decapeptide. 2. Angiotensins were extracted from plasma by adsorption to phenylsilylsilica, and angiotensin I (Ang I) was quantified by radioimmunoassay. The detection limit was 0.77 fmol ml-1, and the extraction recovery of [125I]-Ang I added to albumin buffer was 83% at the inflection point (10 fmol ml-1) of the standard curve. The overall recovery was 98.5 +/- 3.5%. The intra- and inter-assay reproducibility was 10.4% and 9.7% respectively. Cross-reactivity of the antiserum used was low (less than 0.3%) with all angiotensin peptides tested except Ang (2-10) nonapeptide. 3. A human pharmacological model was subsequently used to assess in vivo the biochemical effects of the renin inhibitor CGP 38560A. Six healthy volunteers received 20 mg lisinopril, a long-acting ACE-inhibitor. During the following 24 h, the renin-angiotensin system was reset with typically elevated active plasma renin and Ang I, at respectively 275 and 429% of basal values. 4. In a randomized three-way cross-over protocol, the six volunteers received a 30 min infusion of the renin inhibitor CGP 38560A (125 or 250 micrograms kg-1) or 5% glucose. The fall in plasma Ang I was 92% and 97.5% after the lowest and highest dose of the renin inhibitor, respectively. A concomitant increase in active plasma renin was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Chauveau
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INSERM U367, Paris, France.
Guyenne
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TT
Cumin
F
F
Chatellier
G
G
Corvol
P
P
Ménard
J
J
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D017706:Lisinopril; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011863:Radioimmunoassay; D012016:Reference Values; D000092502:Renin Inhibitors
D000450:Aldosterone; D000803:Angiotensin I; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D017706:Lisinopril; D009842:Oligopeptides; D000092502:Renin Inhibitors; C060150:CGP 38560