Increased plasma renin during renin inhibition. Studies with a novel immunoassay.
The response of renin release to the administration of renin inhibitors cannot be studied with conventional enzymatic methods used to measure plasma renin. In the present experiments, a novel multirange enzyme-linked immunosorbent assay for human and primate renin was used to investigate the changes in plasma immunoreactive renin after renin inhibition. A potent and long-acting statine-containing renin inhibitor, CGP 29 287, was injected in conscious marmosets after mild or severe sodium depletion. In mildly sodium-depleted marmosets, CGP 29 287 (0.1 mg/kg i.v.) reduced mean arterial blood pressure and completely inhibited plasma renin activity for up to 30 minutes. This response was associated with a transient increase in plasma immunoreactive renin concentration. After a dose of 1.0 mg/kg i.v., the reduction of mean arterial pressure and the complete inhibition of plasma renin activity persisted for up to 120 minutes. These effects were accompanied by a sustained increase in plasma immunoreactive renin concentration. In severely sodium-depleted marmosets, CGP 29 287 (1.0 mg/kg i.v.) induced a marked fall in systolic blood pressure and complete inhibition of plasma renin activity within 30 minutes of injection. Plasma immunoreactive renin levels increased to 257% of pretreatment values. The converting-enzyme inhibitor enalaprilat (2 mg/kg i.v.) induced a fall in systolic blood pressure of similar magnitude, which was accompanied by an increase in plasma renin activity. Levels of plasma immunoreactive renin increased to 210% of pretreatment values. Hydralazine (0.2 mg/kg i.v.) did not increase plasma renin activity or plasma immunoreactive renin levels despite a comparable hypotensive effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Hofbauer
K G
KG
Wood
J M
JM
Gulati
N
N
Heusser
C
C
Ménard
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002143:Callitrichinae; D004151:Dipeptides / Q000494:pharmacology; D015773:Enalaprilat; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006830:Hydralazine / Q000494:pharmacology; D007010:Hyponatremia / Q000139:chemically induced; D007106:Immune Sera; D008297:Male; D009842:Oligopeptides; D012083:Renin / Q000097:blood* / Q000276:immunology / Q000494:pharmacology; D000092502:Renin Inhibitors
D004151:Dipeptides; D015773:Enalaprilat; D005665:Furosemide; D006830:Hydralazine; D007106:Immune Sera; D009842:Oligopeptides; D012083:Renin; D000092502:Renin Inhibitors; C045501:CGP 29287