Acute glucocorticoid promotes NHE1 inhibition and cardioprotection against ischemia/reperfusion injury in the rat heart

ESCUDERO, DAIANA; PEREZ NÉSTOR; FANTINELLI, JULIANA; DÍAZ RG; AMARILLO ME

Congreso; SCHCF+ALACF2020 Joint meeting; 2020

Abstract Background/Aims: Glucocorticoid and mineralocorticoid receptors (GR and MR) are highly expressed in cardiac tissue. Glucocorticoids can activate both. While cardiac MR stimulation triggers NHE1 activation, and deleterious intracellular pathways via calcineurin; GR activation ameliorates cardiac dysfunction by calcineurin signaling inactivation. The aim of present work was to investigate the action of glucocorticoids in a rat model of cardiac ischemia/reperfusion injury, and the possible effect on NHE1.Methods: All procedures were approved by the Ethical Committee of Faculty of Medicine (#P-02-03-2017). Acute myocardial infarction (I) was performed in isolated hearts from 5-month-old Wistar rats, by ligation of left anterior descending artery (40min ischemia/60min reperfusion). NHE1 activity was estimate by Na+-dependent pHi recovery from transient acidosis (TA) in isolated papillary muscles. Both experiments were performed in presence or absence of Hydrocortisone (HC), due to its similarity with endogenous cortisol: 10nM for I, and 1nM or 10nM for TA. Proteins phosphorylation and expression were determined by western blot. Data was expressed by mean ± S.E.M., for statistical analysis t-test or ANOVA were conducted.Results: HC reduced infarct size (% of risk area: HCI 9±3 vs. I 37±3, P