CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Hyperosmotic stress promotes NO release in the rat myocardium
LUIS GONANO; JUAN I BURGOS; MALENA MORELL; MARTIN VILA PETROFF
Congreso; 2016 ISHR-Intl World Congress; 2016
Tissue osmolarity is tightly regulated under physiological conditions. However, in different pathological situations as states of severe dehydration, hyperglycemia, hyperlipidemia and diabetes, cardiomyocytes undergo osmotic shrinkage and it is associated with alterations in calcium handling, negative inotropic effects (NIE) and apoptosis.Nitric oxide (NO) synthesized by the nitric oxide synthase (NOS) has been well defined as a second messenger and as a regulator of cardiac function. In a previous study we showed that hyposmotic swelling promotes NO release and that this NO provides contractile support. The aim of this study is to evaluate whether membrane deformation produced by hyperosmotic stress also promotes NO release and to examine the underlying mechanisms involved. We observed that superfusing rat cardiac myocytes, loaded with the NO sensor (DAF-FM), with a hyperosmotic solution (HS:440 mOsm) results in a decrease of cell volume (26%±1.95; n=21) and a significant increase in fluorescence of DAF-FM (10%±2.55; n=22) compared to myocytes superfused with an isosmotic solution (IS: 309 mOsm; n=10). When cells are superfused with HS+L-NAME (inhibitor of NOS), HS+Nitroguanidine (NG: inhibitor of NOS1) or HS+Wortmaninn (WT: inhibitor of NOS3) cell volume decreases in absence of NO release suggesting that NOS1 and NOS3 are responsible for NO release during hyperosmotic stress. Supporting the involvement of NOS1 and NOS3 in hyperosmotic stress-induced NO release, Western blot analysis showed an increase in NOS1 and NOS3 activity (pNOS1 and pNOS3) in hearts perfused with hyperosmotic solution compared with hearts perfused with isosmotic solution.These results suggest that NOS1 and NOS3 promote NO release during hyperosmotic stress. This NO release could impact on altered cell function observed in pathological situations associated with hyperosmotic stress.