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

MEDINA AJ; YEVES AM; ENNIS IL; BURGOS, JI

Ciudad Autónoma de Buenos Aires

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

International Society of Heart Reserch

CARDIOPROTECTIVEEFFECT OF IGF-1 UPON THE HYPERTROPHIED MYOCARDIUM OF THE SPONTANEOUSLYHYPERTENSIVE RATS (SHR): A KEY ROLE ON CARDIAC Na+/H+ EXCHANGER (NHE-1) ACTIVITY AND OXIDATIVE STRESS. Alejandra M. Yeves; Juan I. Burgos; Andrés J. Medina;Irene L. Ennis. Centro de Investigaciones Cardiovasculares, Facultad deCiencias Médicas, UNLP-CONICET, Argentina. Oxidative stress and NHE-1 hyperactivity areinterrelated phenomena that play a key role in pathological but not in exercise-induced cardiachypertrophy (CH). We have demonstrated that IGF-1, released during exercise training,throughAKT inhibits NHE-1 and that a swimmingroutine transformed pathological into physiological CH in the SHR. Therefore, we hypothesize thatIGF-1 by preventing NHE-1 hyperactivity and oxidative stress could be responsiblefor the cardioprotective effect of training in SHR. NHE-1 activity incardiomyocytes (proton efflux mmol/L/min) monitored by BCECF-AM epifluorescencewas significantly reduced by IGF-1 (2.03±0.47, n=7), effect prevented byAG1024, an antagonist of IGF-1 receptor (3.71±0.9, n=7) and by the AKTinhibitor MK2206 (4.01±0.65, n=12). Similarly, IGF-1 significantly reduced H2O2production 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). Theantioxidant action of IGF-1 was accompanied by a significant increase in theactivity of superoxide dismutase (SOD) catalase (IGF-1: 20±1.5, n=7 and 44.9±3.6N=5 vs. control: 14.5±1.6, n=5 and 34±2.3, n=7, U/mg, respectively). Interestinglythe beneficial effects of IGF-1 correlated with higher cardiac contractilityrevealed 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<0.05). Since thebioactive peptide apelin, up-regulated by training, may increase cardiaccontractility and was proposed to exert antioxidant effects, we quantified itsmRNA abundance and that of its receptor APJ in our experimental conditions findingthat IGF-1 significantly increased both (IGF-1: 251±48 and 184±29 vs. control:100±6.2 and 100±15.9, apelin and APJ respectively).In summary, our resultssuggest that the inhibition of NHE-1 hyperactivity as well as the antioxidant effectof IGF-1, probably by apelin-mediated increase in SOD and catalase activity, representbeneficial cardiac adaptations leading to the physiological phenotype in theSHR subjected to exercise training.