Myocardial ischemic tolerance in rats subjected to endurance exercise training during adaptation to chronic hypoxia
Abstrakt
Chronic hypoxia and exercise are natural stimuli that confer sustainable cardioprotection against ischemia-reperfusion (I/R) injury, but it is unknown whether they can act in synergy to enhance ischemic resistance. Inflammatory response mediated by tumor necrosis factor-alpha (TNF-alpha) plays a role in the infarct size limitation by continuous normobaric hypoxia (CNH), whereas exercise is associated with anti-inflammatory effects.
This study was conducted to determine if exercise training performed under conditions of CNH (12% O-2) affects myocardial ischemic resistance with respect to inflammatory and redox status. Adult male Wistar rats were assigned to one of the following groups: normoxic sedentary, normoxic trained, hypoxic sedentary, and hypoxic trained.
ELISA and Western blot analysis, respectively, were used to quantify myocardial cytokines and the expression of TNF-alpha receptors, nuclear factor-kappa B (NF-kappa B), and selected components of related signaling pathways. Infarct size and arrhythmias were assessed in open-chest rats subjected to I/R.
CNH increased TNF-alpha and interleukin-6 levels and the expression of TNF-alpha type 2 receptor, NF-kappa B, inducible nitric oxide synthase (iNOS), cytosolic phospholipase A(2)alpha, cyclooxygenase-2, manganese superoxide dismutase (MnSOD), and catalase. None of these effects occurred in the normoxic trained group, whereas exercise in hypoxia abolished or significantly attenuated CNH-induced responses, except for NF-kappa B, iNOS, and MnSOD.
Both CNH and exercise reduced infarct size, but their combination provided the same degree of protection as CNH alone. In conclusion, exercise training does not amplify the cardioprotection conferred by CNH.
High ischemic tolerance of the CNH hearts persists after exercise, possibly by maintaining the increased antioxidant capacity despite attenuating TNF-alpha-dependent protective signaling.