Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: Impact on swelling-induced negative inotropic effect
Aims Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias.We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on sw...
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| Autores principales: | , , , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
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2014
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/85202 |
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I19-R120-10915-85202 |
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dspace |
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Universidad Nacional de La Plata |
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I-19 |
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R-120 |
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SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Médicas Contractile dysfunction Hypotonic swelling Ischaemia reperfusion Nitric oxide |
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Ciencias Médicas Contractile dysfunction Hypotonic swelling Ischaemia reperfusion Nitric oxide Gonano, Luis Alberto Morell, Malena Burgos, Juan Ignacio Dulce, Raúl Ariel De Giusti, Verónica Celeste Aiello, Ernesto Alejandro Hare, J. M. Vila Petroff, Martín Gerardo Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: Impact on swelling-induced negative inotropic effect |
| topic_facet |
Ciencias Médicas Contractile dysfunction Hypotonic swelling Ischaemia reperfusion Nitric oxide |
| description |
Aims Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias.We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. Methods and results Superfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient, and increased NO-sensitive 4-amino-5-methylamino-2', 7'-difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mMof theNOsynthase inhibitor L-NAME, cell swelling occurred in the absence of NOrelease. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-inducedNOrelease. The swelling-induced negative inotropic effectwas exacerbated in the presence of either L-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca2+ release. Conclusions Our findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling. |
| format |
Articulo Articulo |
| author |
Gonano, Luis Alberto Morell, Malena Burgos, Juan Ignacio Dulce, Raúl Ariel De Giusti, Verónica Celeste Aiello, Ernesto Alejandro Hare, J. M. Vila Petroff, Martín Gerardo |
| author_facet |
Gonano, Luis Alberto Morell, Malena Burgos, Juan Ignacio Dulce, Raúl Ariel De Giusti, Verónica Celeste Aiello, Ernesto Alejandro Hare, J. M. Vila Petroff, Martín Gerardo |
| author_sort |
Gonano, Luis Alberto |
| title |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: Impact on swelling-induced negative inotropic effect |
| title_short |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: Impact on swelling-induced negative inotropic effect |
| title_full |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: Impact on swelling-induced negative inotropic effect |
| title_fullStr |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: Impact on swelling-induced negative inotropic effect |
| title_full_unstemmed |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: Impact on swelling-induced negative inotropic effect |
| title_sort |
hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect |
| publishDate |
2014 |
| url |
http://sedici.unlp.edu.ar/handle/10915/85202 |
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