Autor: |
Trond Brattelid, Eirik Qvigstad, Lise R Moltzau, Silje V S Bekkevold, Dagny L Sandnes, Jon Arne K Birkeland, Tor Skomedal, Jan-Bjørn Osnes, Ivar Sjaastad, Finn Olav Levy |
Jazyk: |
angličtina |
Rok vydání: |
2012 |
Předmět: |
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Zdroj: |
PLoS ONE, Vol 7, Iss 9, p e45489 (2012) |
Druh dokumentu: |
article |
ISSN: |
1932-6203 |
DOI: |
10.1371/journal.pone.0045489 |
Popis: |
A positive inotropic responsiveness to serotonin, mediated by 5-HT(4) and 5-HT(2A) receptors, appears in the ventricle of rats with post-infarction congestive heart failure (HF) and pressure overload-induced hypertrophy. A hallmark of HF is a transition towards a foetal genotype which correlates with loss of cardiac functions. Thus, we wanted to investigate whether the foetal and neonatal cardiac ventricle displays serotonin responsiveness. Wistar rat hearts were collected day 3 and 1 before expected birth (days -3 and -1), as well as day 1, 3, 5 and 113 (age matched with Sham and HF) after birth. Hearts from post-infarction HF and sham-operated animals (Sham) were also collected. Heart tissue was examined for mRNA expression of 5-HT(4), 5-HT(2A) and 5-HT(2B) serotonin receptors, 5-HT transporter, atrial natriuretic peptide (ANP) and myosin heavy chain (MHC)-α and MHC-β (real-time quantitative RT-PCR) as well as 5-HT-receptor-mediated increase in contractile function exvivo (electrical field stimulation of ventricular strips from foetal and neonatal rats and left ventricular papillary muscle from adult rats in organ bath). Both 5-HT(4) mRNA expression and functional responses were highest at day -3 and decreased gradually to day 5, with a further decrease to adult levels. In HF, receptor mRNA levels and functional responses reappeared, but to lower levels than in the foetal ventricle. The 5-HT(2A) and 5-HT(2B) receptor mRNA levels increased to a maximum immediately after birth, but of these, only the 5-HT(2A) receptor mediated a positive inotropic response. We suggest that the 5-HT(4) receptor is a representative of a foetal cardiac gene program, functional in late foetal development and reactivated in heart failure. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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