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

GODOY COTO JOSHUA; CALDIZ CI; CAVALLI FIORELLA; YEVES AM; PEREYRA ERICA; ENNIS IL

Atenas

Otro; 2019 ESH SUMMER SCHOOL; 2019

European Society of Hypertension

Background:Hypertensive cardiac hypertrophy is characterized by structural and functionalalterations 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 keysevents. Regular exercise training, probably through inducing the release ofhumoral factors such as insulin like growth factor 1 (IGF-1) and apelin, favorsmitochondrial adaptations. However, the underlying subcellular mechanisms contributingto exercise induced- mitochondrial adaptation are not fully elucidated yet. Aim: Todetermine whether a swimming routine improves the mitochondrial phenotype inthe myocardium of the spontaneously hypertensive rats (SHR). Moreover, wehypothesize that acute exposure to physiological concentrations of apelin orIGF-1 can mimick the beneficial effect of exercise training on mitochondria. Methods: Ratswere randomly assigned to a sedentary (Sed) or swim-trained (Swim) group.Training sessions consisted of 90-min twice daily swimming periods, fivedays/week during 8 weeks. On the other hand, in vitro experiments wereperformed in isolated cardiomyocytes of non-trained SHR incubated with IGF-1 orapelin (10 and 50 nmol/L, respectively). Results are expressed as mean±S.E.Mfrom 2 or more independent experiments and the statistical significance testedby t-test or ANOVA.Results: The swimmingroutine significantly enhanced citrate synthase activity in soleus muscle, supportingthe success of the aerobic training. Electronic microscopy revealed an improvedarrangement of mitochondria in the myocardium of exercised SHR, that were alsolarger than those of Sed (area in μm2, Swim: 0.7±0.02 n=351 vs Sed: 0.52±0.018n=346). Moreover, the ΔΨm (measured in isolated mitochondria loaded withRhodamine 123) was improved by swimming  (inmV, Swim: -173.04±2.09, n=15 vs. Sed: -155.13±6.3, n=11) fact that correlatedwith 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 (measuredby 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 themyocardial expression of apelin and its receptor APJ and PGC1-α, suggestingmitochondrial biogenesis. In isolated cardiac mitochondria from sedentary SHRwe found that apelin and IGF-1 prevent the loss of ΔΨm induced by the exposureto 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 modulatethe detrimental impact of oxidative stress on mitochondrial. Conclusions: Theimpairment of the mitochondrial phenotype characteristic of the myocardium fromSHR is able to be improved through a swimming routine, being IGF-1 and apelin putativemediators of the adaptive mitochondrial phenotype.