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Tumour necrosis factor‐ α contributes to improved cardiac ischaemic tolerance in rats adapted to chronic continuous hypoxia
Author(s) -
Chytilová A.,
Borchert G. H.,
MandíkováAlánová P.,
Hlaváčková M.,
Kopkan L.,
Khan Md. A. Hye,
Imig J. D.,
Kolář F.,
Neckář J.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12489
Subject(s) - malondialdehyde , medicine , oxidative stress , nitrotyrosine , tumor necrosis factor alpha , infliximab , hypoxia (environmental) , endocrinology , nitric oxide synthase , necrosis , nitric oxide , chemistry , oxygen , organic chemistry
Aim It has been demonstrated that tumour necrosis factor‐alpha ( TNF ‐ α ) via its receptor 2 ( TNFR 2) plays a role in the cardioprotective effects of preconditioning. It is also well known that chronic hypoxia is associated with activation of inflammatory response. With this background, we hypothesized that TNF ‐ α signalling may contribute to the improved ischaemic tolerance of chronically hypoxic hearts. Methods Adult male Wistar rats were kept either at room air (normoxic controls) or at continuous normobaric hypoxia ( CNH ; inspired O 2 fraction 0.1) for 3 weeks; subgroups of animals were treated with infliximab (monoclonal antibody against TNF ‐ α ; 5 mg kg −1 , i.p., once a week). Myocardial levels of oxidative stress markers and the expression of selected signalling molecules were analysed. Infarct size (tetrazolium staining) was assessed in open‐chest rats subjected to acute coronary artery occlusion/reperfusion. Results CNH increased myocardial TNF ‐ α level and expression of TNFR 2; this response was abolished by infliximab treatment. CNH reduced myocardial infarct size from 50.8 ± 4.3% of the area at risk in normoxic animals to 35.5 ± 2.4%. Infliximab abolished the protective effect of CNH (44.9 ± 2.0%). CNH increased the levels of oxidative stress markers (3‐nitrotyrosine and malondialdehyde), the expression of nuclear factor κ B and manganese superoxide dismutase, while these effects were absent in infliximab‐treated animals. CNH ‐elevated levels of inducible nitric oxide synthase and cyclooxygenase 2 were not affected by infliximab. Conclusion TNF ‐ α plays a role in the induction of ischaemia‐resistant cardiac phenotype of CNH rats, possibly via the activation of protective redox signalling.