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-α (TNF-α) 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 whether exercise training performed under conditions of CNH (12% O2) affects myocardial ischemic resistance with respect to inflammatory and redox status. Adult male Wistar rats were assigned to one of following groups: normoxic sedentary, normoxic trained, hypoxic sedentary, and hypoxic trained. ELISA and Western blot, respectively, were used to quantify myocardial cytokines and the expression of TNF-α receptors, nuclear factor-κB (NF-κB) and selected components of related signaling pathways. Infarct size and arrhythmias were assessed in open-chest rats subjected to I/R. CNH increased TNF-α and interleukin-6 levels and the expression of TNF-α type 2 receptor, NF-κB, inducible nitric oxide synthase (iNOS), cytosolic phospholipase A2α, cyclooxygenase-2, manganese superoxide dismutase (MnSOD) and catalase. None of these effects occurred in normoxic trained group, whereas exercise in hypoxia abolished or significantly attenuated CNH-induced responses, except for NF-κB, 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-α-dependent protective signaling.
- chronic hypoxia
- exercise training
- Copyright © 2016, Journal of Applied Physiology