| The effect of recombinant aminopeptidase A on hypertension in spontaneously hypertensive rats: its effect in comparison with candesartan. | |
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MedLine Citation:
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PMID: 18726831 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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An understanding of aminopeptidase A in hypertension is important, given its ability to cleave the N-terminal aspartic acid of potent vasoconstrictor angiotensin II. However, the role of aminopeptidase A in hypertension has received limited attention. Because we have succeeded in producing recombinant human aminopeptidase A, the effect of aminopeptidase A on systolic blood pressure in the spontaneously hypertensive rat was examined. Aminopeptidase A of 0.016 mg/kg was administrated intravenously to spontaneously hypertensive rats and blood pressure was monitored for 72 h. For repeated administration, aminopeptidase A doses of 0.016 mg/kg and 0.1-mg/kg doses of candesartan (an angiotensin II receptor 1 subtype blocker) were administrated daily in spontaneously hypertensive rats and blood pressure was monitored for 5 d. Bolus intravenous injection of aminopeptidase A at a dose of 0.016 mg/kg significantly decreased systolic blood pressure for 36 h in spontaneously hypertensive rats. A comparison of the antihypertensive effects of aminopeptidase A versus candesartan in spontaneously hypertensive rats showed that the effective dose of aminopeptidase A was about one-tenth that of candesartan. These results suggest the novel approach of utilizing aminopeptidase A to treat hypertension by degrading circulating angiotensin II before it binds to the receptor 1 subtype. |
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Authors:
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M Ishii; A Hattori; Y Numaguchi; M Tsujimoto; S Ishiura; H Kobayashi; T Murohara; J-W Wright; S Mizutani |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-22 |
Journal Detail:
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Title: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme Volume: 40 ISSN: 0018-5043 ISO Abbreviation: Horm. Metab. Res. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-14 Completed Date: 2009-03-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0177722 Medline TA: Horm Metab Res Country: Germany |
Other Details:
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Languages: eng Pagination: 887-91 Citation Subset: IM |
Affiliation:
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Department of Medical Science of Proteases, Nagoya University School of Medicine, Nagoya, Japan. masai@med.nagoya-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin I
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blood Angiotensin II / blood Angiotensin II Type 1 Receptor Blockers / pharmacology* Animals Antihypertensive Agents* Baculoviridae / genetics Benzimidazoles / pharmacology* Blood Pressure / drug effects Genetic Vectors Glutamyl Aminopeptidase / genetics, pharmacology* Humans Hypertension / drug therapy* Male Mutation Nitroprusside / pharmacology Rats Rats, Inbred SHR Rats, Inbred WKY Recombinant Proteins / pharmacology Tetrazoles / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Recombinant Proteins; 0/Tetrazoles; 11128-99-7/Angiotensin II; 139481-59-7/candesartan; 15078-28-1/Nitroprusside; 9041-90-1/Angiotensin I; EC 3.4.11.7/Glutamyl Aminopeptidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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