| Comparative effects of three different potent renin inhibitors in primates. | |
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MedLine Citation:
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PMID: 8319997 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J P Clozel; W Fischli |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article |
Journal Detail:
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Title: Hypertension Volume: 22 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1993 Jul |
Date Detail:
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Created Date: 1993-08-05 Completed Date: 1993-08-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 9-17 Citation Subset: IM |
Affiliation:
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Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Oral Angiotensin II / blood Animals Blood Pressure / drug effects Cilazapril / administration & dosage, pharmacology Dipeptides / administration & dosage, pharmacology* Drug Interactions Heart Rate / drug effects Humans Imidazoles / administration & dosage, pharmacology* Injections, Intravenous Oligopeptides / administration & dosage, pharmacology* Renin / antagonists & inhibitors*, blood Renin-Angiotensin System / drug effects* Saimiri Time Factors |
| Chemical | |
Reg. No./Substance:
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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 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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