Renin release regulation during acute renin inhibition in normal volunteers.
Blockade of the renin-angiotensin system by an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II (Ang II) antagonist is accompanied by a reactive rise in renin release. This rise is generally attributed to interruption of the short feedback loop between Ang II and renin release. Similarly, after the administration of a renin inhibitor, the plasma concentrations of active and total renin are increased and plasma renin activity is suppressed. The aim of the present study was to investigate if a fall in the plasma Ang II level is the unique determinant of the rise in the active renin (AR) level that follows renin inhibition. Six normal male volunteers participated in three successive 240-minute experiments at weekly intervals according to a single-blind randomized Latin square design. For experiment 1, Ang II was infused at 2 ng/kg/min from 0 to 60 minutes and at 4 ng/kg/min from 60 to 120 minutes. For experiment 2, 0.3 mg/kg of the new potent renin inhibitor Ro 42-5892 was injected at 30 minutes followed by infusion at 0.1 mg/kg/hr from 30 to 240 minutes. For experiment 3, Ang II and Ro 42-5892 were administered simultaneously at the same doses as described above. The mean +/- SEM Ang II concentration increased from 10.2 +/- 1.6 to 33.7 +/- 11.2 pg/ml after infusion of exogenous peptide. It decreased from 9.5 +/- 0.9 to 1.4 +/- 0.3 pg/ml after the injection of Ro 42-5892 and increased from 15.6 +/- 2.9 to 37.1 +/- 11.8 pg/ml after the simultaneous infusion of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
Ménard
J
J
INSERM U36, Paris, France.
Guyene
T T
TT
Chatellier
G
G
Kleinbloesem
C H
CH
Bernadet
P
P
D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles; D007262:Infusions, Intravenous; D008297:Male; D012083:Renin / Q000097:blood* / Q000494:pharmacology; D000092502:Renin Inhibitors
D000450:Aldosterone; D000803:Angiotensin I; D000804:Angiotensin II; D007093:Imidazoles; D012083:Renin; D000092502:Renin Inhibitors; C065581:remikiren