CONICET | Buscador de Institutos y Recursos Humanos

Diabetic cardiomyopathy described as ventricular dysfunction occurring in diabetic (DM) patients may not be attributable to underlying coronary artery disease and hypertension. This cardiac contractile dysfunction could be associated to mitochondrial dysfunction. The aim of this work was to study heart mitochondrial function of diabetic rats, 4 weeks after streptozotocin injection (60 mg/kg, i.p.), focusing on the role of nitric oxide (NO) in mitochondrial biogenesis. Diabetic hearts showed lower contractile response (40%) after a β-adrenergic stimulus than control animals and an attenuated decrease in the isovolumic relaxation time (Δt50C = -26%; Δt50DM = -11%) indicating an impairment in the lusitropic reserve (55%). Tissue O2 consumption was also declined (15%) in DM in comparison with control animals. Cytochrome oxidase activity measured in heart homogenates indicates that the mitochondrial mass per heart mass was 45% higher in DM than in control animals. This effect was confirmed by electron microscope images that showed an increase in the mitochondria number (94%) and in the mitochondrial area per total area (33%) in diabetic hearts, suggesting that DM leads to mitochondrial biogenesis. However, mitochondrial state 3 O2 consumption (22%), respiratory control ratio (25%), mitochondrial respiratory complexes activities (I-III, 22%; II-III, 30% and IV, 22%) and ATP production (40%) were decreased in DM hearts. Moreover, an enhancement in mitochondrial NO production (23%) and mtNOS expression were observed in diabetic rat hearts. These results show a mitochondrial dysfunction with an enhancement in mitochondrial biogenesis, in which NO may be involved. This process could be triggered in response to hyperglycemia and could explain the cardiac energy metabolism impairment that occurs in hearts of diabetic rats.