Heart Failure Reviews

, Volume 13, Issue 3, pp 339–353 | Cite as

Role of central and peripheral aminopeptidase activities in the control of blood pressure: a working hypothesis

  • Manuel Ramírez
  • Isabel Prieto
  • Francisco Alba
  • Francisco Vives
  • Inmaculada Banegas
  • Marc de Gasparo


Although there is a large body of knowledge on protein synthesis, the available data on protein catabolism, although quite substantial, are still inadequate. This is due to the marked differences in the activity of proteolytic enzymes, compounded by different substrate specificities and multiple environmental factors. Understanding enzyme behavior under physiological and pathological conditions requires the identification of specific proteolytic activities, such as aminopeptidases, as able to degrade certain peptidergic hormones or neuropeptides. Another requirement is the isolation, purification and characterization of the enzymes involved. In addition, systematic studies are needed to determine each enzyme’s subcellular location, tissue distribution, and the influence of environmental factors such as diurnal rhythm, age, gender, diet, cholesterol, or steroids. Central and peripheral aminopeptidases may play a role in the control of blood pressure by coordinating the effect of the different peptides of the renin–angiotensin system cascade, acting through the AT1, AT2, and AT4 receptors. Our review of the available data suggests the hypothesis that cholesterol or steroids, particularly testosterone, significantly influence aminopeptidase activities, their substrate availability and consequently their functions. These observations may have relevant clinical implications for a better understanding of the pathophysiology of cardiovascular diseases, and thus for their treatment with aminopeptidase inhibitors.


Aminopeptidases Cardiovascular diseases Cholesterol Dietary fat Environmental factors Gender Steroids Testosterone 



Angiotensin-converting enzyme




Arginyl aminopeptidase


Aspartyl aminopeptidase


Arginine vasopressin


Cystinyl aminopeptidase


Glomerular filtration rate


Glutamyl aminopeptidase


High-density lipoproteins


Low-density lipoproteins


Leucyl aminopeptidase


Monounsaturated fatty acids


Polyunsaturated fatty acids


Renin–angiotensin system


Saturated fatty acids


Spontaneously hypertensive rats


Tumor necrosis factor



This work was supported by the Junta de Andalucía through grants PAI CVI-221 (Peptides and Peptidases) and CTS 438 (Group for Neurological Diseases Research in Southern Spain). We thank K. Shashok for improving the use of English in the manuscript.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Manuel Ramírez
    • 1
  • Isabel Prieto
    • 1
  • Francisco Alba
    • 2
  • Francisco Vives
    • 2
  • Inmaculada Banegas
    • 1
  • Marc de Gasparo
    • 3
  1. 1.Unit of Physiology, Department of Health SciencesUniversity of JaénJaenSpain
  2. 2.Institute of Neurosciences of GranadaUniversity of GranadaGranadaSpain
  3. 3.MG Consulting Co.RossemaisonSwitzerland

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