CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Hypotonic swelling promotes nitric oxide release in rat cardiac myoyctes: Impact on swelling-induced negative inotropic effect
LUIS GONANO; MALENA MORELL; MARTIN GERARDO VILA PETROFF
Congreso; XX Annual Meeting of the International Society for Heart Research Latin American Section; 2012
HYPOTONIC SWELLING PROMOTES NITRIC OXIDE RELEASE IN RAT CARDIAC MYOYCTES: IMPACT ON SWELLING-INDUCED NEGATIVE INOTROPIC EFFECT. Luis Gonano, Malena Morell and Martin Vila Petroff. Centro de Investigaciones Cardiovasculares CCT-CONICET. Facultad de Cs. Médicas, UNLP. 60 y 120 La Plata, Argentina. Cell swelling occurs in multiple pathological situations and in particular, it has been shown to contribute to the deleterious effects of ischemia and reperfusion by promoting contractile dysfunction and predisposing the heart for arrhythmias. We have previously shown that myocyte axial stretch promotes nitric oxide (NO) release. However, whether myocyte swelling promotes NO release and if so, whether it impacts on swelling-induced contractile dysfunction has not been previously assessed. We found that treating rat cardiac myocytes, loaded with the NO sensor DAF-2, with a hypotonic solution, increased cell volume, reduced myocyte contraction amplitude and significantly increased DAF-2 fluorescence. When cells were exposed to the hypotonic solution supplemented with 2.5 mM of the NO synthase inhibitor L-Name, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also inhibited by the PI3K inhibitor Wortmannin. Interestingly, swelling-induced negative inotropic effect was exacerbated in the presence of L-Name or Wortmannin. These results suggest that swelling activates NOS3 (NOS3 being a known target of the PI3K/AKT axis in contrast to NOS1) which promotes NO release. Taken together, these findings suggest a novel mechanism for NO release in cardiac myocytes with putative pathophysiological relevance in the context of ischemia and reperfusion, where it may serve a cardioprotective role by reducing the extent of swelling-induced contractile dysfunction.