Salmon cardiac peptide as a model for natriuretic peptide secretion : the role of mechanical load, temperature and endothelin-1
1University of Oulu, Faculty of Medicine, Department of Physiology
2University of Oulu, Biocenter Oulu
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|Persistent link:|| http://urn.fi/urn:isbn:9514282000
|Publish Date:|| 2006-09-19
|Thesis type:||Doctoral Dissertation
|Defence Note:||Academic dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in Auditorium F101 of the Department of Physiology (Aapistie 7), on September 29th, 2006, at 12 noon
Docent Mika Laine
Professor Mikko Nikinmaa
The natriuretic peptides are a family of hormones secreted by the heart. They play a fundamental role in salt and water balance and blood pressure regulation. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are the known members of the mammalian natriuretic peptide family. A major stimulus for the secretion of cardiac natriuretic peptides is myocyte stretch. Therefore, the secretion of natriuretic peptides is increased in response to elevated blood volume. Natriuretic peptide production and release is also affected by several other factors, such as endothelin-1 (ET-1), acting in paracrine fashion.
The aim of this study was to elucidate factors regulating the novel cardiac peptide hormone, salmon cardiac peptide (sCP), belonging to the family of natriuretic peptides. The role of mechanical load, temperature and ET-1 in sCP secretion and production was studied using in vitro (isolated perfused ventricle preparation) and in vivo methods. Comparisons between the natriuretic peptide systems in fish and mammals were done to clarify functional evolution of this hormone family. Salmon (Salmo salar) was selected as a model, since it has an outstanding adaptability to wide variations in environmental salinity and has developed defence mechanisms against volume or salt load.
The results showed that salmon ventricle stores large amounts of the prohormone of sCP, whereas the secreted form is the mature 29-amino acid form. The N-terminal fragment of pro-sCP is co-secreted with sCP in equimolar amounts. sCP is released rapidly in response to appropriate stimulus, whereas induction of its gene expression is slower. Mechanical load is an important regulator of sCP secretion. Temperature also plays a major role in regulating sCP plasma concentration by affecting its elimination from circulation. Additionally, ET-1 is a potent secretagogue of the sCP system and an inotropic agent in salmon heart. Furthermore, the present results reveal remarkable synergism between the cardiac effects of ET-1 and β-adrenergic stimulation.
In conclusion, the sCP system in salmon ventricle largely resembles the ANP system in mammalian atrium, while also having specific characteristics, such as a regulated ventricular natriuretic peptide secretion pathway. Therefore, the sCP system offers a unique model for studying mechanisms of natriuretic peptide biology.
Acta Universitatis Ouluensis. D, Medica
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