Abstract 18348: Exercise Training Mitigates Oxidative Stress and Restores Nitric Oxide Production in the Diabetic Heart
Introduction: Diabetic metabolic derangement (DMD) is associated with increased myocardial oxidative stress (OS) and left ventricular (LV) dysfunction. Here we tested the hypothesis that exercise training (ET) ameliorates myocardial OS and improves LV and small artery function in DMD.
Methods: DMD was produced in adult male Göttingen miniswine by streptozotocin injections and high fat diet while control animals (CON) remained on normal pigchow. At 3-month (mo) follow-up, swine were randomized into 2-month exercise training (ET) on a treadmill 3-times per week or remained untrained (UT), ultimately resulting in 5mo of study and four study groups (Table).
Results: Robust DMD developed, evidenced by hyperglycemia (glucose >12 mmol/l), hypercholesterolemia (>5.9 mmol/l in DMD vs. ~1.1 mmol/l in CON) and hypertriglyceridemia, which was associated with an impaired E/É ratio as assessed repeatedly by echocardiography. DMD also resulted in perturbations in nitroso-redox balance in the LV, due to increased superoxide production and eNOS uncoupling (monomer/dimer ratio), resulting in reduced LV NO production (Table). ET improved maximal aerobic fitness markedly (~80%) and similarly in both CON-ET and DMD-ET, but did not significantly affect blood glucose and lipid profiles or E/É ratio. ET blunted DMD-induced OS and recoupled eNOS, thereby restoring NO production (Table). These ET-induced changes were accompanied by improvements in endothelium-dependent relaxation to bradykinin in skeletal muscle resistance arteries, although ET failed to restore endothelium-independent relaxation to nitroprusside in small coronary arteries.
Conclusion: DMD results in myocardial OS and diastolic LV dysfunction, and although exercise training does not improve global LV or small coronary artery function in diabetes, it does partially restore the myocardial nitroso-redox balance.
Author Disclosures: I. Heinonen: None. O. Sorop: None. B. van Dalen: None. V. de Beer: None. Y. Octavia: None. R. van Duin: None. L. Blonden: None. D. Merkus: None. D. Duncker: None.
- © 2016 by American Heart Association, Inc.