We used the secretion of the novel salmon cardiac peptide (sCP) as a model to examine the mechanisms of ventricular hormone release. Mechanical load increased dose dependently the secretion of immunoreactive sCP from isolated perfused salmon ventricle, with 3. 3-fold increase when a load of 13 cmH(2)O was applied. Endothelin-1 (5 nmol/l) was also able to rapidly increase the secretion of sCP. The released peptide corresponded to the biologically active sCP-29, whereas the large ventricular storage consisted of pro-sCP-sized material. With the use of immunoelectron microscopy, a large number of granules containing immunoreactive sCP could be detected in salmon ventricle. As judged by RNA blot analysis, there was very active basal expression of the sCP gene in the ventricle, which was not increased by mechanical load of up to 2-h duration. Our results show that the ventricle actively expresses the gene of sCP, stores the prohormone in secretory granules, and releases the peptide in response to mechanical load and endothelin-1. Thus the salmon ventricle uses the regulated pathway to produce and release a hormone structurally related to the mammalian natriuretic peptides.

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.

To find out the significance of the newest member of the natriuretic peptide family, salmon cardiac peptide (sCP), we have determined the distribution of the peptide and its mRNA as well as the tissue and plasma molecular forms in several teleosts. Using probes based on the salmon sCP cDNA in Northern blot analysis we found mRNA homologous to that of sCP to be present in the heart of 15 fish species representing nine different genera. We developed a specific RIA for the salmon 29 amino acid peptide to be able to study the distribution of the peptide in the heart and plasma of different fish species. Despite the probable interspecies differences in the peptide sequence, large quantities of immunoreactive sCP were found in the atrium, ventricle and plasma of most of the fish species studied, suggesting that a cardiac hormone homologous to sCP has an endocrine function in a large variety of teleost species. The molecular form of the hormone secreted and stored in the tissue was determined by gel filtration high pressure liquid chromatography. In salmon, as in most of the other fish species studied, the predominant immunoreactive sCP in plasma corresponded to the low molecular weight form, with a size similar to that of the biologically active 29 amino acid sCP (sCP-29), whereas the form stored in the heart corresponded to the high molecular weight pro-sCP-sized material. The form secreted by isolated perfused salmon ventricle, in the basal state as well as when mechanically loaded, was the sCP-29-sized peptide, thus ruling out the possibility that the conversion from high to low molecular weight material is caused by plasma proteases. In conclusion, sCP-like peptides are produced and secreted from the heart of a large number of different fish species. Their post-translational processing appears to be remarkably similar to that of mammalian atrial natriuretic peptide.

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.

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