Abstract
Natriuretic peptide hormones secreted from the heart are important in
maintaining
the volume and electrolyte balance and in regulation of blood pressure. The
secretion of natriuretic peptides is stimulated by myocyte stretch and paracrine
factors. However, the intracellular actions of these stimuli and the cellular and
molecular mechanisms involved in the processing and secretion of natriuretic
peptides are still largely unknown. In this study, a new model for studies of the
natriuretic peptide system was developed using a novel natriuretic peptide from
salmon.
Salmon (Salmo salar) maintains its water and salt
homeostasis despite the volume gain in fresh water and electrolyte gain in sea
water. Thus, salmon is an ideal model to study the mechanisms regulating the
extracellular volume and salt balance, like natriuretic peptides. Furthermore,
comparative studies revealing the common characteristics in phylogenetically
distinct species suggest the importance of these factors in the regulation of the
natriuretic peptide system.
A novel natriuretic peptide, salmon cardiac peptide (sCP), was cloned from
salmon
heart. Distribution of sCP was studied in a variety of vertebrates and its
physiological effects were examined in in vitro and
in vivo experiments in salmon and rats. The storage and
release of sCP was studied using a salmon ventricle perfusion system and by
analysing the molecular forms of stored and secreted forms. Factors modulating
the secretion and circulating concentration of sCP, and cardiac peptide and sCP
mRNA level in salmon were examined as well.
The biosynthesis of sCP is strictly restricted to the heart. sCP is stored
in
myocytes in the prohormone form, while the secreted form is a 29-amino acid
peptide in salmon. Mechanical load on isolated salmon ventricle and volume
overload in intact salmon induced a rapid release of sCP. Exposure to
hyperosmotic environment decreased the plasma sCP level. sCP increased diuresis
and natriuresis, as well as relaxed preconstricted arteries from salmon and rats.
Thus the storage, processing and release of sCP resembles those of mammalian ANP.
The circulating level of sCP in salmon was markedly upregulated at increased
temperatures. Upregulation resulted from decreased elimination rather than
increased secretion of sCP, providing the first direct evidence that elimination
is used for the regulation of the natriuretic peptide system. In conclusion, sCP
is a promising model for studying the general factors regulating the cardiac
natriuretic peptides.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-6493-2 |
| Date | 18 September 2001 |
| Creators | Tervonen, V. (Virpi) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 2001 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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