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Investigation of the biochemical effects of renin inhibition in normal volunteers treated by an ACE inhibitor.
Author(s) -
Chauveau D,
Guyenne TT,
Cumin F,
Chatellier G,
Corvol P,
Menard J
Publication year - 1992
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1992.tb04032.x
Subject(s) - renin–angiotensin system , lisinopril , chemistry , renin inhibitor , plasma renin activity , endocrinology , in vivo , radioimmunoassay , medicine , ace inhibitor , enzyme inhibitor , angiotensin ii , angiotensin converting enzyme , pharmacology , enzyme , biochemistry , biology , receptor , blood pressure , microbiology and biotechnology
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)