Olgar 2018 MiP2018
Aging in humans represents downhill processes in cardio-protective systems and mitochondria plays pivotal role due to the higher energy demanding during senescence [1,2]. We aimed to analyse how mitochondrial targeted antioxidants affects key mechanisms that are responsible for contractile function in aging subjects.
In this study 6- and 24- month old male wistar rats were used. Heart functions examined with Langerdorff-perfusion system. Fluorescence examination performed with confocal imaging and microspectrofluorometry. Membrane currents monitored with patch-clamp recordings.
MitoTEMPO antioxidant capacity evaluated with amount of intracellular reactive species [ROS]in in freshly isolated cardiomyocytes. Aged cardiomyocytes exhibited remarkable recovery of [ROS]in following 1-h MitoTEMPO (0.1 µM) incubation. MitoTEMPO were also restored elevated cytosolic Ca2+, Na+, Zn2+ levels together with mitochondrial membrane potential (MMP) in aged cardiomyocytes. During aging ATP-dependent K+-currents (KATP) reduced but MitoTEMPO fully restored these currents in aged cardiomyocytes. The left ventricular developed pressure (LVDP) was significantly depressed in aged-rats. Following MitoTEMPO (0.1 µM) perfusion of hearts for 1-h preserved depressed contractile activity (LVDP) in aged-rats. Phenylephrine induced contractions in isolated aortic rings was significantly less in aged-rats compared to those of young-rats. MitoTEMPO treatment of aortic rings induced significant increases in the depressed contractile activity in aged-aortic rings. Similarly, precontracted aortic rings showed reduced Ach-induced vasorelaxation responses in the aged-aortic rings and MitoTEMPO treatment of aortic rings induced significant improvement in aged-aortic rings.
In summary present data demonstrated that improvement of mitochondrial antioxidant capacity with MitoTEMPO, directly targeting mitochondrial reactive oxygen species, could preserve vascular, electrical and contractile function of cardiovascular systems in elderly subjects.
Labels: MiParea: mt-Medicine, Pharmacology;toxicology Pathology: Aging;senescence
Organism: Rat Tissue;cell: Heart
- Dept Biophysics, Fac Med, Ankara Uni, Turkey. - [email protected]
- Di Lisa F, Bernardi P (2005) Mitochondrial function and myocardial aging. A critical analysis of the role of permeability transition. Cardiovasc Res 66:222-32.
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