Cardioprotective effect of IGF-1 upon the hypertrophied myocardium of the spontaneously hypertensive rats (SHR): a key role on cardiac Na+/H+ exchanger (NHE-1) activity and oxidative stress

YEVES AM; BURGOS JI; MEDINA AJ; ENNIS IL

Buenos Aires

Congreso; International Society for Heart Research XXII World Congress (ISHR); 2016

International Society for Heart Research

Oxidative stress and NHE-1 hyperactivity are interrelated phenomena that play a key role in pathological but not in exercise-induced cardiac hypertrophy (CH). We have demonstrated that IGF-1, released during exercise training, through AKT inhibits NHE-1 and that a swimming routine transformed pathological into physiological CH in the SHR. Therefore, we hypothesize that IGF-1 by preventing NHE-1 hyperactivity and oxidative stress could be responsible for the cardioprotective effect of training in SHR. NHE-1 activity in cardiomyocytes (proton efflux mmol/L/min) monitored by BCECF-AM epifluorescence was significantly reduced by IGF-1 (2.03±0.47, n=7), effect prevented by AG1024, an antagonist of IGF-1 receptor (3.71±0.9, n=7) and by the AKT inhibitor MK2206 (4.01±0.65, n=12). Similarly, IGF-1 significantly reduced H2O2 production in cardiomyocytes loaded with DCF-DA (IGF-1: -3.63±1.1; n=7, IGF-1 + AG1024: 6.06±3.4, n=7; control: 5.12±2.5, n=12, AU after 10 min incubation). The antioxidant action of IGF-1 was accompanied by a significant increase in the activity of superoxide dismutase (SOD) catalase (IGF-1: 20±1.5, n=7 and 44.9±3.6 N=5 vs. control: 14.5±1.6, n=5 and 34±2.3, n=7, U/mg, respectively). Interestingly the beneficial effects of IGF-1 correlated with higher cardiac contractility revealed by an increase in cardiomyocyte shortening (IGF-1: 145.8±14, n=5 vs. control: 96.8±5, n=3, % at 10 min respect to time 0, p