Document Detail


The effect of recombinant aminopeptidase A on hypertension in spontaneously hypertensive rats: its effect in comparison with candesartan.
MedLine Citation:
PMID:  18726831     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M Ishii; A Hattori; Y Numaguchi; M Tsujimoto; S Ishiura; H Kobayashi; T Murohara; J-W Wright; S Mizutani
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-22
Journal Detail:
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:
Created Date:  2008-11-14     Completed Date:  2009-03-05     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  0177722     Medline TA:  Horm Metab Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  887-91     Citation Subset:  IM    
Affiliation:
Department of Medical Science of Proteases, Nagoya University School of Medicine, Nagoya, Japan. masai@med.nagoya-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Angiotensin I / 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:
0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Recombinant Proteins; 0/Tetrazoles; 11128-99-7/Angiotensin II; 15078-28-1/Nitroprusside; 9041-90-1/Angiotensin I; EC 3.4.11.7/Glutamyl Aminopeptidase; S8Q36MD2XX/candesartan

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


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