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

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Abstract

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.

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Abbreviations

ACE:

Angiotensin-converting enzyme

Ang:

Angiotensin

ArgAP:

Arginyl aminopeptidase

AspAP:

Aspartyl aminopeptidase

AVP:

Arginine vasopressin

CysAP:

Cystinyl aminopeptidase

GFR:

Glomerular filtration rate

GluAP:

Glutamyl aminopeptidase

HDL:

High-density lipoproteins

LDL:

Low-density lipoproteins

LeuAP:

Leucyl aminopeptidase

MUFA:

Monounsaturated fatty acids

PUFA:

Polyunsaturated fatty acids

RAS:

Renin–angiotensin system

SAFA:

Saturated fatty acids

SHR:

Spontaneously hypertensive rats

TNF:

Tumor necrosis factor

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Acknowledgments

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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Authors and Affiliations

  1. Unit of Physiology, Department of Health Sciences, University of Jaén, Jaen, 23071, Spain

    Manuel Ramírez, Isabel Prieto & Inmaculada Banegas

  2. Institute of Neurosciences of Granada, University of Granada, Granada, Spain

    Francisco Alba & Francisco Vives

  3. MG Consulting Co., Rue es Planches 5, Rossemaison, Switzerland

    Marc de Gasparo

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  1. Manuel Ramírez
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  2. Isabel Prieto
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  3. Francisco Alba
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  4. Francisco Vives
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  5. Inmaculada Banegas
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  6. Marc de Gasparo
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Correspondence to Manuel Ramírez.

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Ramírez, M., Prieto, I., Alba, F. et al. Role of central and peripheral aminopeptidase activities in the control of blood pressure: a working hypothesis. Heart Fail Rev 13, 339–353 (2008). https://doi.org/10.1007/s10741-007-9066-6

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