Hypoxia regulates the natriuretic peptide system.

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 hemoconcentration and ultimately to the increased oxygen-carrying capacity of unit volume of blood.