Title : Non-neuronal cholinergic machinery present in cardiomyocytes offsets hypertrophic signals - Rocha-Resende_2012_J.Mol.Cell.Cardiol_53_206 |
Author(s) : Rocha-Resende C , Roy A , Resende R , Ladeira MS , Lara A , de Morais Gomes ER , Prado VF , Gros R , Guatimosim C , Prado MAM , Guatimosim S |
Ref : Journal of Molecular & Cellular Cardiology , 53 :206 , 2012 |
Abstract :
Recent work has provided compelling evidence that increased levels of acetylcholine (ACh) can be protective in heart failure, whereas reduced levels of ACh secretion can cause heart malfunction. Previous data show that cardiomyocytes themselves can actively secrete ACh, raising the question of whether this cardiomyocyte derived ACh may contribute to the protective effects of ACh in the heart. To address the functionality of this non-neuronal ACh machinery, we used cholinesterase inhibitors and a siRNA targeted to AChE (acetylcholinesterase) as a way to increase the availability of ACh secreted by cardiac cells. By using nitric oxide (NO) formation as a biological sensor for released ACh, we showed that cholinesterase inhibition increased NO levels in freshly isolated ventricular myocytes and that this effect was prevented by atropine, a muscarinic receptor antagonist, and by inhibition of ACh synthesis or vesicular storage. Functionally, cholinesterase inhibition prevented the hypertrophic effect as well as molecular changes and calcium transient alterations induced by adrenergic overstimulation in cardiomyocytes. Moreover, inhibition of ACh storage or atropine blunted the anti-hypertrophic action of cholinesterase inhibition. Altogether, our results show that cardiomyocytes possess functional cholinergic machinery that offsets deleterious effects of hyperadrenergic stimulation. In addition, we show that adrenergic stimulation upregulates expression levels of cholinergic components. We propose that this cardiomyocyte cholinergic signaling could amplify the protective effects of the parasympathetic nervous system in the heart and may counteract or partially neutralize hypertrophic adrenergic effects. |
PubMedSearch : Rocha-Resende_2012_J.Mol.Cell.Cardiol_53_206 |
PubMedID: 22587993 |
Rocha-Resende C, Roy A, Resende R, Ladeira MS, Lara A, de Morais Gomes ER, Prado VF, Gros R, Guatimosim C, Prado MAM, Guatimosim S (2012)
Non-neuronal cholinergic machinery present in cardiomyocytes offsets hypertrophic signals
Journal of Molecular & Cellular Cardiology
53 :206
Rocha-Resende C, Roy A, Resende R, Ladeira MS, Lara A, de Morais Gomes ER, Prado VF, Gros R, Guatimosim C, Prado MAM, Guatimosim S (2012)
Journal of Molecular & Cellular Cardiology
53 :206