AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress

In different pathological situations, cardiac cells undergo hyperosmotic stress (HS) and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. Given that nitric oxide (NO) is a well-recognized modulator of cardiac contractility and cell survi...

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Autores principales: Morell, Malena, Burgos Migone, Juan Ignacio, Gonano, Luis Alberto, Vila Petroff, Martín Gerardo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Medicina
Hyperosmotic stress
Nitric oxide
AMPK
Contractile dysfunction
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/136191
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-136191
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
Hyperosmotic stress
Nitric oxide
AMPK
Contractile dysfunction
spellingShingle Medicina
Hyperosmotic stress
Nitric oxide
AMPK
Contractile dysfunction
Morell, Malena
Burgos Migone, Juan Ignacio
Gonano, Luis Alberto
Vila Petroff, Martín Gerardo
AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
topic_facet Medicina
Hyperosmotic stress
Nitric oxide
AMPK
Contractile dysfunction
description In different pathological situations, cardiac cells undergo hyperosmotic stress (HS) and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. Given that nitric oxide (NO) is a well-recognized modulator of cardiac contractility and cell survival, we evaluated whether HS increases NO production and its impact on the negative inotropic effect observed during this type of stress. Superfusing cardiac myocytes with a hypertonic solution (HS: 440 mOsm) decreased cell volume and increased NO-sensitive DAF-FM fluorescence compared with myocytes superfused with an isotonic solution (IS: 309 mOsm). When cells were exposed to HS in addition to different inhibitors: L-NAME (NO synthase inhibitor), nitroguanidine (nNOS inhibitor), and Wortmannin (eNOS inhibitor) cell shrinkage occurred in the absence of NO release, suggesting that HS activates nNOS and eNOS. Consistently, western blot analysis demonstrated that maintaining cardiac myocytes in HS promotes phosphorylation and thus, activation of nNOS and eNOS compared to myocytes maintained in IS. HS-induced nNOS and eNOS activation and NO production were also prevented by AMPK inhibition with Dorsomorphin (DORSO). In addition, the HS-induced negative inotropic effect was exacerbated in the presence of either L-NAME, DORSO, ODQ (guanylate cyclase inhibitor), or KT5823 (PKG inhibitor), suggesting that NO provides contractile support via a cGMP/PKG-dependent mechanism. Our findings suggest a novel mechanism of AMPK-dependent NO release in cardiac myocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hyperosmotic stress.
format Articulo
Articulo
author Morell, Malena
Burgos Migone, Juan Ignacio
Gonano, Luis Alberto
Vila Petroff, Martín Gerardo
author_facet Morell, Malena
Burgos Migone, Juan Ignacio
Gonano, Luis Alberto
Vila Petroff, Martín Gerardo
author_sort Morell, Malena
title AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_short AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_full AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_fullStr AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_full_unstemmed AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_sort ampk-dependent nitric oxide release provides contractile support during hyperosmotic stress
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/136191
work_keys_str_mv AT morellmalena ampkdependentnitricoxidereleaseprovidescontractilesupportduringhyperosmoticstress
AT burgosmigonejuanignacio ampkdependentnitricoxidereleaseprovidescontractilesupportduringhyperosmoticstress
AT gonanoluisalberto ampkdependentnitricoxidereleaseprovidescontractilesupportduringhyperosmoticstress
AT vilapetroffmartingerardo ampkdependentnitricoxidereleaseprovidescontractilesupportduringhyperosmoticstress
bdutipo_str Repositorios
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