A novel cardiac hormone related to A-, B- and C-type natriuretic peptides

Abstract

Mechanisms acting against accumulation of volume are important in pathophysiological situations with volume and salt overload, such as congestive heart failure. Osmoregulating animals that migrate between environments with high and low salinity are ideal models for studying the defence mechanisms against volume gain. We have now cloned and sequenced from salmon (Salmo salar) a cDNA encoding a novel vasorelaxant cardiac hormone of 29 amino acids which is produced by proteolytic processing of a 148-residue preprohormone. Structural and biological results, as well as its distribution indicate that it belongs to an unrecognized family related to natriuretic peptides, perhaps representing an ancestor of ANP and BNP. We have synthesized the 29-amino acid hormone and set up a specific radioimmunoassay. The distribution of the mRNA and peptide is strictly restricted to the heart, with high levels both in the atrium and ventricle in various fish species. The hormone relaxes aortic smooth muscle derived from salmon at nanomolar concentrations. Its release from isolated perfused salmon ventricle is very sensitive to mechanical load: a 10 mmHg load induces a rapid 5-fold increase in hormone release. Our results indicate that the novel cardiac hormone has an important role in fish volume regulation. They also demonstrate that mechanical stimuli have been central to volume regulation since early evolution.