Heart Failure Reviews

, Volume 13, Issue 3, pp 273–284

New insights into the importance of aminopeptidase A in hypertension

Authors

  • Shigehiko Mizutani
    • Department of Medical Science of ProteasesNagoya University, Graduate School of Medicine
    • Department of Medical Science of ProteasesNagoya University, Graduate School of Medicine
  • Akira Hattori
    • Laboratory of Cellular BiochemistryRIKEN (The Institute of Physical and Chemical Research)
  • Seiji Nomura
    • Department of Obstetrics and GynecologyNagoya University, Graduate School of Medicine
  • Yasushi Numaguchi
    • Department of Medical Science of ProteasesNagoya University, Graduate School of Medicine
  • Masafumi Tsujimoto
    • Laboratory of Cellular BiochemistryRIKEN (The Institute of Physical and Chemical Research)
  • Hiroshi Kobayshi
    • Department of Obstetrics and GynecologyNara Medical University
  • Toyoaki Murohara
    • Departments of Cardiology and Vascular SurgeryNagoya University, Graduate School of Medicine
  • John W. Wright
    • Departments of Psychology and Veterinary PhysiologyWashington State University
Article

DOI: 10.1007/s10741-007-9065-7

Cite this article as:
Mizutani, S., Ishii, M., Hattori, A. et al. Heart Fail Rev (2008) 13: 273. doi:10.1007/s10741-007-9065-7

Abstract

The renin-angiotensin system (RAS) plays an important role in the maintenance of normal blood pressure and the etiology of hypertension; however, minimal attention has been paid to the degradation of the effector peptide, angiotensin II (AngII). Since aminopeptidase A (APA)-deficient mice develop hypertension APA appears to be an essential enzyme in the control of blood pressure via degradation of AngII. The robust hypertension seen in the spontaneously hypertensive rat (SHR) is due to activation of the RAS, and an accompanying decrease in kidney APA. Changes in APA have also been measured during the activation of the RAS in the Goldblatt hypertension model and Dahl salt-sensitive (DSS) rat. The DSS rat shows an elevation in renal APA activity at the onset of hypertension suggesting a protective role against elevations in circulating AngII, followed by decreased APA activity with advancing hypertension. Changes seen in human maternal serum APA activity during preeclampsia are similar to changes measured in renal APA in the DSS rat model. APA activity is higher than during normal pregnancy at the onset of preeclampsia, and with advancing preeclampsia (severe preeclampsia) declines below that seen during normal pregnancy. Serum APA activity is also increased during hormone replacement therapy (HRT), perhaps in reaction to elevated levels of AngII. Thus, it appears important to consider the relationship among activation of the RAS, circulating levels of AngII, and the availability of APA in hypertensive disorders.

Keywords

Angiotensin IIAminopeptidase AHypertensive ratsPreeclampsiaHormone replacement therapy

Abbreviations

ACE

Angiotensin-converting enzyme

ACE2

Angiotensin-converting enzyme 2

APA

Aminopeptidase A

APN

Aminopeptidase N

AP

Area postrema

ARB

AT1 receptor blocker

AT1R

AT1 receptor

AT2R

AT2 receptor

AngI

Angiotensin I

AngII

Angiotensin II

AngIII

Angiotensin III

AngIV

Angiotensin IV

CVOs

Circumventricular organs

DSR

Dahl Salt-resistant

DSS

Dahl Salt-sensitive

HF

Acute heart failure

HRT

Hormone replacement Therapy

icv

Intracerebroventricular

NTS

Nucleus of the solitary tract

OVLT

Organum vasculosum of the lamina terminalis

PVN

Paraventricular nucleus

RAS

Renin-angiotensin system

SFO

Subfornical organ

SHR

Spontaneously hypertensive rat

SON

Supraoptic nucleus

WKY

Wistar-Kyoto

2K1C

Two-kidney one-clip

Copyright information

© Springer Science+Business Media, LLC 2007