Horm Metab Res 2008; 40(12): 887-891
DOI: 10.1055/s-0028-1083783
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

The Effect of Recombinant Aminopeptidase A on Hypertension in Spontaneously Hypertensive Rats: Its Effect in Comparison with Candesartan

M. Ishii 1 , A. Hattori 2 , Y. Numaguchi 1 , M. Tsujimoto 2 , S. Ishiura 3 , H. Kobayashi 4 , T. Murohara 5 , J.-W. Wright 6 , S. Mizutani 1
  • 1Department of Medical Science of Proteases (Goodman), Nagoya University School of Medicine, Nagoya, Japan
  • 2Laboratory of Cellular Biochemistry, RIKEN, Saitama, Japan
  • 3Department of Life Science, Graduate School of Arts and Science, University of Tokyo, Japan
  • 4Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan
  • 5Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • 6Departments of Psychology and Veterinary Physiology, Washington State University, Pullman, Washington, USA
Further Information

Publication History

received 19.12.2007

accepted 20.05.2008

Publication Date:
22 August 2008 (online)

Abstract

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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Correspondence

M. IshiiMD 

Department of Medical Science of Proteases

Nagoya University School of Medicine

65 Tsurumai-cho

Showa-ku

Nagoya 466-8550

Japan

Phone: +81/52/744 22 65

Fax: +81/52/744 22 65

Email: masai@med.nagoya-u.ac.jp