Hypotonic Swelling Promotes Nitric Oxide Release in Rat Cardiac Ventricular Myoycte: Impact on Swelling-Induced Negative Inotropic Effect

MALENA MORELL, LUIS GONANO, MARISA SEPÚLVEDA AND MARTIN VILA PETROFF

New London

Congreso; Gordon research conference: cardiac regulatory mechanisms; 2012

Gordon Conferences

Cell swelling is known to contribute to the pathophysiology of ischemia and reperfusion by promoting contractile dysfunction and predisposing the heart for arrhythmias. However, the underlying subcellular mechanisms of swelling-induced contractile dysfunction are still not fully understood. We have previously shown that cardiac cell stretch promotes nitric oxide (NO) release favoring spontaneous SR Ca2+ release. Here we investigate whether hypotonic swelling promotes nitric oxide release and if so, whether it contributes to cardiac cell swelling-induced contractile dysfunction. 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. Interestingly, swelling-induced negative inotropic effect was exacerbated in the presence of L-Name. These results suggest that hypotonic swelling promotes NO release which reduces contractile dysfunction. 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 contractile dysfunction.