Abstract | BACKGROUND:
Oxytocin (OT) and functional OT receptor (OTR) are expressed in the heart and are involved in blood pressure regulation and cardioprotection. Cardiac OTR signaling is associated with atrial natriuretic peptide ( ANP) and nitric oxide (NO) release. During the synthesis of OT, its precursor, termed OT- Gly-Lys-Arg ( OT-GKR), is accumulated in the developing rat heart. Consequently, we hypothesized that an OT-related mechanism of ANP controls cardiomyocyte (CM) hypertrophy. METHODS: The experiments were carried out in newborn and adult rat CM cultures. The enhanced protein synthesis and increased CM volume were mediated by a 24-h treatment with endothelin-1 or angiotensin II. RESULTS: The treatment of CM with OT or its abundant cardiac precursor, OT-GKR, revealed ANP accumulation in the cell peri-nuclear region and increased intracellular cGMP. Consequently, the CM hypertrophy was abolished by the treatment of 10nM OT or 10nM OT-GKR. The ANP receptor antagonist ( anantin) and NO synthases inhibitor ( l-NAME) inhibited cGMP production in CMs exposed to OT. STO-609 and compound C inhibition of anti-hypertrophic OT effects in CMs indicated the contribution of calcium- calmodulin kinase kinase and AMP-activated protein kinase pathways. Moreover, in ET-1 stimulated cells, OT treatment normalized the reduced Akt phosphorylation, prevented abundant accumulation of ANP and blocked ET-1-mediated translocation of nuclear factor of activated T-cells (NFAT) into the cell nuclei. CONCLUSION: cGMP/ protein kinase G mediates OT-induced anti-hypertrophic response with the contribution of ANP and NO. OT treatment represents a novel approach in attenuation of cardiac hypertrophy during development and cardiac pathology.
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Authors | Ahmed Menaouar, Maria Florian, Donghao Wang, Bogdan Danalache, Marek Jankowski, Jolanta Gutkowska |
Journal | International journal of cardiology
(Int J Cardiol)
Vol. 175
Issue 1
Pg. 38-49
(Jul 15 2014)
ISSN: 1874-1754 [Electronic] Netherlands |
PMID | 24852833
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
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Topics |
- Animals
- Animals, Newborn
- Cardiomegaly
(drug therapy, pathology)
- Cell Differentiation
(drug effects, physiology)
- Cell Enlargement
(drug effects)
- Cells, Cultured
- Dose-Response Relationship, Drug
- Male
- Myocytes, Cardiac
(drug effects, metabolism, pathology)
- Oxytocin
(pharmacology, therapeutic use)
- Rats
- Rats, Sprague-Dawley
- Treatment Outcome
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