Document Detail

Comparative effects of three different potent renin inhibitors in primates.
MedLine Citation:
PMID:  8319997     Owner:  NLM     Status:  MEDLINE    
The goal of the present study was to compare the effects of three potent reference renin inhibitors (remikiren, CGP 38560A, and enalkiren) in sodium-depleted normotensive squirrel monkeys. In these monkeys, arterial pressure was measured in the conscious state with a telemetry system. Oral and intravenous maximal effective doses of the three renin inhibitors were compared in parallel groups of monkeys. In additional experiments, remikiren was given on top of either CGP 38560A or enalkiren in the same animals. Finally, the three drugs were compared with the angiotensin converting enzyme inhibitor cilazapril. The effects of the three drugs on the plasma components of the renin-angiotensin system (plasma renin activity, immunoreactive renin, and immunoreactive angiotensin II concentrations) were also measured. Our results show that remikiren was as effective as cilazapril and markedly more effective than CGP 38560A or enalkiren in reducing arterial pressure in our monkey model. Interestingly, these differences in arterial pressure could not be explained by differences of in vitro potency or different biochemical changes of the plasma components of the renin-angiotensin system, because the inhibitors all reduced immunoreactive angiotensin II to similarly low levels. One possible explanation is that, in our model, remikiren in contrast to CGP 38560A and enalkiren is able to inhibit renin in a functionally important extraplasmatic compartment.
J P Clozel; W Fischli
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  Hypertension     Volume:  22     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1993 Jul 
Date Detail:
Created Date:  1993-08-05     Completed Date:  1993-08-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9-17     Citation Subset:  IM    
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
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MeSH Terms
Administration, Oral
Angiotensin II / blood
Blood Pressure / drug effects
Cilazapril / administration & dosage,  pharmacology
Dipeptides / administration & dosage,  pharmacology*
Drug Interactions
Heart Rate / drug effects
Imidazoles / administration & dosage,  pharmacology*
Injections, Intravenous
Oligopeptides / administration & dosage,  pharmacology*
Renin / antagonists & inhibitors*,  blood
Renin-Angiotensin System / drug effects*
Time Factors
Reg. No./Substance:
0/Dipeptides; 0/Imidazoles; 0/Oligopeptides; 11128-99-7/Angiotensin II; 113082-98-7/enalkiren; 122088-76-0/CGP 38560; 135669-48-6/remikiren; 92077-78-6/Cilazapril; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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