IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2011;3(3):191-201.

Review Article
Hypoxia regulates the natriuretic peptide system

Olli Arjamaa, Mikko Nikinmaa

Center of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, Finland

Received July 28, 2011; accepted August 10, 2011; Epub September 6, 2010; Published September 30, 2011

Abstract: Numerous clinical studies have addressed the role of the natriuretic peptide system either as a diagnostic tool or as a guide
to treatment in many cardiac diseases. The concept behind these studies has been that intravascular overload produces cardiac wall
stress that alone stimulates the synthesis and release of natriuretic peptides the result of which is diuresis, natriuresis, and
vasodilatation. However, almost thirty years after the discovery of the natriuretic peptides the measurement of these peptides,
especially the BNP, has not met all the expectations of a simple and useful diagnostic tool in clinical cardiology, possibly due to
confounding factors confusing the interpretation of the wall stress effect. In the same way as in pressure studies, it has been shown
that hypoxia is a direct and sufficient stimulus for the synthesis and release of ANP and BNP. Additionally, hypoxia-response elements
have been characterized from the promoter sequence of both the ANP and the BNP genes. Furthermore, a physiological rhythm
(eupnea-apnea), causing changes in blood oxygen tension, regulates the plasma levels of ANP in sleeping seal pups which are
spontaneously able to hold back their breathing. We suggest, on the basis of the extensive published literature, that the stimulus for the
synthesis and release of natriuretic peptides is the oxygen gradient which always occurs in all human tissues in physiological
conditions. The plasma volume contraction caused by natriuretic peptides (natriuresis, diuresis, and plasma shift) leads to
haemoconcentration and ultimately to the increased oxygen-carrying capacity of unit volume of blood. (IJPPP1107005).

Keywords: Hypoxia, natriuretic peptides, hemoconcentration

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Address all correspondence to:
Olli Arjamaa, MD, PhD
Department of Biology
20014 University of Turku
Phone: +358 405125452
E-mail: olli.arjamaa@utu.fi