Physiology of natriuretic peptides: The volume overload hypothesis revisited.

The discovery of the natriuretic peptide system in the early 1980s aroused great interest among clinical cardiologists. The heart was not a mechanical pump alone, but also an endocrine organ that had powerful effects on blood circulation. Natriuretic peptides caused both natriuresis and diuresis, and they responded to a volume overload which caused either stretch or pressure on the heart. As a result, the findings led to the conclusion that the human body had a hormone with effects similar to those of a drug which treats high blood pressure. Later, it became evident that the volume contraction was fortified by extrarenal plasma shift. Here, a hypothesis is presented in which the role of natriuretic peptides is to regulate oxygen transport as the volume contraction leads to hemoconcentration with an increased oxygen-carrying capacity. Wall stress, either chemical or mechanical, changes the oxygen gradient of the myocardium and affects the diffusion of oxygen within a myocyte. In support of this hypothesis, hypoxia-response elements have been found in both the atrial natriuretic peptide and the brain natriuretic peptide genes.