MITOCHONDRIAL ADAPTATIONS INDUCED BY SWIMMNING IN THE MYOCARDIUM OF SPONTANEUSLY HYPERTENSIVE RATS: ROLE OF IGF-1 AND APELIN

YEVES, ALEJANDRA; PEREYRA, ERICA; GODOY COTO, JOSHUA; CALDIZ, CLAUDIA; CAVALLI, FIORELLA; ENNIS, IRENE

Brauron, Atenas

Otro; 2019 ESH SUMMER SCHOOL; 2019

Sociedad Europea de Hipertensión Arterial

MITOCHONDRIAL ADAPTATIONS INDUCED BY SWIMMNING IN THE MYOCARDIUM OF SPONTANEUSLY HYPERTENSIVE RATS: ROLE OF IGF-1 AND APELINBackground: Hypertensive cardiac hypertrophy is characterized by structural and functional alterations on the mitochondria. Variations in the mitochondrial membrane potential (ΔΨm), the open probability of the permeability transition pore (mPTP), oxidative stress, mitochondrial dynamic and calcium handling are some of the keys events. Regular exercise training, probably through inducing the release of humoral factors such as insulin like growth factor 1 (IGF-1) and apelin, favors mitochondrial adaptations. However, the underlying subcellular mechanisms contributing to exercise induced- mitochondrial adaptation are not fully elucidated yet. Aim: To determine whether a swimming routine improves the mitochondrial phenotype in the myocardium of the spontaneously hypertensive rats (SHR). Moreover, we hypothesize that acute exposure to physiological concentrations of apelin or IGF-1 can mimick the beneficial effect of exercise training on mitochondria. Methods: Rats were randomly assigned to a sedentary (Sed) or swim-trained (Swim) group. Training sessions consisted of 90-min twice daily swimming periods, five days/week during 8 weeks. On the other hand, in vitro experiments were performed in isolated cardiomyocytes of non-trained SHR incubated with IGF-1 or apelin (10 and 50 nmol/L, respectively). Results are expressed as mean±S.E.M from 2 or more independent experiments and the statistical significance tested by t-test or ANOVA.Results: The swimming routine significantly enhanced citrate synthase activity in soleus muscle, supporting the success of the aerobic training. Electronic microscopy revealed an improved arrangement of mitochondria in the myocardium of exercised SHR, that were also larger than those of Sed (area in μm2, Swim: 0.7±0.02 n=351 vs Sed: 0.52±0.018 n=346). Moreover, the ΔΨm (measured in isolated mitochondria loaded with Rhodamine 123) was improved by swimming (in mV, Swim: -173.04±2.09, n=15 vs. Sed: -155.13±6.3, n=11) fact that correlated with myocardial citrate synthase activity (in μmol citrate min-1mg-1, Swim: 0.87±0.03 n=5 vs. Sed: 0.638±0.044 n= 6,). Mitochondrial calcium content (measured by Calcium Green 5N) significantly increased with swimming (in mmol/mg protein, 2.99±0.31 n=2 vs Swim: 72.2±11.3, n=7). Training also up regulated the myocardial expression of apelin and its receptor APJ and PGC1-α, suggesting mitochondrial biogenesis. In isolated cardiac mitochondria from sedentary SHR we found that apelin and IGF-1 prevent the loss of ΔΨm induced by the exposure to H2O2 (F/F0: Control: 0.84±0.03, n=22; apelin: 0.99±0.02 n=13, IGF-1: 0.92±0.02 n=27), suggesting that these hormones can modulate the detrimental impact of oxidative stress on mitochondrial. Conclusions: The impairment of the mitochondrial phenotype characteristic of the myocardium from SHR is able to be improved through a swimming routine, being IGF-1 and apelin putative mediators of the adaptive mitochondrial phenotype.