MYOCARDIAL IGF-1 TARGETS IN ACUTE AND CHRONIC TREATMENT OF HYPERTENSIVE RATS

GODOY COTO J; PEREYRA EV; ENNIS IL

Congreso; Reunión anual de la Sociedad Argentina de Fisiología (SAFIS); 2023

MYOCARDIAL IGF-1 TARGETS IN ACUTE AND CHRONIC TREATMENT OF HYPERTENSIVE RATS (R88)Godoy Coto J1, Pereyra EV1, Ennis IL1 Centro de Investigaciones Cardiovasculares ?Dr. Horacio E. Cingolani?, Facultad de Ciencias Médicas, UNLP ? CONICET.Introduction: Essential hypertension promotes oxidative stress and mitochondrial dysfunction. Exercise promotes cardioprotection in part due to increased IGF-1 plasma levels. Whether IGF-1 affects the mitochondria phenotype in an acute/chronic way is still unknown. Objectives: To determine the beneficial effects of exercise/IGF-1 on the mitochondria and reactive oxygen species production in the hypertensive myocardium in both chronic and acute models. Methods: Spontaneously hypertensive rats (SHR) were randomized into sedentary (S) or trained by 8-week swimming routine (T) groups. Also, SHR cardiomyocytes were exposed for 15 min to 10 nM IGF-1 with/without an IGF1R antagonist (100nM AG1024). mRNA and phosphorylation levels, ROS production, and mitochondrial membrane potential (ΔΨm) were quantified in left ventricle, isolated mitochondria, and cardiomyocytes. Results are shown as mean±SEM (n) and statistically different, otherwise p-value is stated. Normality was assessed and t-tests or two-way ANOVA were performed. Results: Chronic model. Training increased IGF1R (%S, T: 144.4±18.5 (6)), but not IGF-1 mRNA; diminished ROS production both in left ventricle ((%S, T: 63.74±7.26 (11)) and energized mitochondria (F/min*mg, S: 0.0090±0.0006 (5), T: 0.0038±0.0009 (5)); enhanced ΔΨm (mV, S: -157.6±9.2 (5), T: 183.6±2.9 (5)); and it also increased the phosphorylation of Akt (%S, T: 123.4±6.3 (5)) and its downstream target GSK3β (%S, T: 159.1±22.1 (10)). Acute model. Basal ROS production was not changed by IGF-1 with/without AG1024. H2O2-induced ROS production was prevented by IGF-1 (F/min, 0.0017±0.0006 (6)) but not in the presence of AG1024 (F/min, 0.0025±0.008(6)). Mild mitochondrial depolarization (FCCP 500 nM) did not change ROS production. Mild oxidative stress had no effect on ΔΨm. Mitochondrial depolarization was not avoided by acute IGF-1 treatment. Conclusion: Training -probably through IGF-1- improved oxidative stress and ΔΨm in SHR myocardium. Acute IGF-1 treatment prevented cardiomyocyte ROS damage but not mitochondrial insult. IGF1R/Akt/GSK3β pathway seems to be the responsible for ROS protection, but other pathways might be involved in mitochondrial improvement. TOPIC AREA: CARDIOVASCULAR PHYSIOLOGY-HYPERTENSION