Novel strategies are needed that can stimulate endogenous signaling pathways to protect the heart from myocardial infarction. The present study tested the hypothesis that appropriate regimen of cold acclimation (CA) may provide a promising approach for improving myocardial resistance to ischemia/reperfusion (I/R) injury without negative side effects. We evaluated myocardial I/R injury, mitochondrial swelling, and β-adrenergic receptor (β-AR)-adenylyl cyclase-mediated signaling. Male Wistar rats were exposed to CA (8°C, 8 h/day for a week, followed by 4 wk at 8°C for 24 h/day), while the recovery group (CAR) was kept at 24°C for an additional 2 wk. The myocardial infarction induced by coronary occlusion for 20 min followed by 3-h reperfusion was reduced from 56% in controls to 30% and 23% after CA and CAR, respectively. In line, the rate of mitochondrial swelling at 200 μM Ca2+ was decreased in both groups. Acute administration of metoprolol decreased infarction in control group and did not affect the CA-elicited cardiprotection. Accordingly, neither β1-AR-Gsα-adenylyl cyclase signaling, stimulated with specific ligands, nor p-PKA/PKA ratios were affected after CA or CAR. Importantly, Western blot and immunofluorescence analyses revealed β2- and β3-AR protein enrichment in membranes in both experimental groups. We conclude that gradual cold acclimation results in a persisting increase of myocardial resistance to I/R injury without hypertension and hypertrophy. The cardioprotective phenotype is associated with unaltered adenylyl cyclase signaling and increased mitochondrial resistance to Ca2+-overload. The potential role of upregulated β2/β3-AR pathways remains to be elucidated.NEW & NOTEWORTHY We present a new model of mild gradual cold acclimation increasing tolerance to myocardial ischemia/reperfusion injury without hypertension and hypertrophy. Cardioprotective phenotype is accompanied by unaltered adenylyl cyclase signaling and increased mitochondrial resistance to Ca2+-overload. The potential role of upregulated β2/β3-adrenoreceptor activation is considered. These findings may stimulate the development of novel preventive and therapeutic strategies against myocardial ischemia/reperfusion injury.
The impact of repeated exposure to cold and cold adaptation on human cardiovascular health is not fully understood. The aim of the study was to determine the effect of cold adaptation on cardiovascular risk factors, thyroid hormones and the capacity of humans to reset the damaging effect of oxidative stress. Ten well cold-adapted winter swimmers (CA) and 16 non-adapted controls (CON) were enroled in this experiment to test whether cold adaptation could influence the parameters of lipoprotein metabolism, cholesterol efflux capacity (CEC), homocysteine, thyroid hormones, antioxidant defence markers (reduced glutathione (GSH), glutathione peroxidase 1 (GPX1), glutathione reductase (GR), catalase (CAT) and paraoxonase 1 (PON1)) and oxidative stress markers (concentration of conjugated dienes (CD)). A decreased apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio was found in the CA group (p<0.05), but other lipoprotein parameters, including CEC, did not differ significantly. Plasma homocysteine was lower in CA subjects in comparison with controls (p<0.05). Higher triiodothyronine (T3) values were observed in the CA compared to the CON (p<0.05) group, but TSH and other thyroid hormones did not differ between both groups. CA subjects had lower activity of GPX1 (p<0.05), lower concentrations of CD (p<0.05) and increased activities of PON1 (p<0.001) compared to CON subjects. A trend for decreased activity of CAT (p=0.06) in CA compared to CON groups was also observed, but GSH levels did not differ significantly. Zn concentration was higher in the CA group than in the CON group (p<0.001). Human cold adaptation can influence oxidative stress markers. Trends towards the improvement of cardiovascular risk factors in cold-adapted subjects also indicate the positive effect of cold adaptation on cardio-protective mechanisms.
- MeSH
- antioxidancia metabolismus MeSH
- ateroskleróza epidemiologie patofyziologie MeSH
- dospělí MeSH
- fyziologická adaptace fyziologie MeSH
- hormony štítné žlázy metabolismus MeSH
- hormony krev MeSH
- kardiovaskulární nemoci epidemiologie patofyziologie MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolismus lipidů MeSH
- nízká teplota * MeSH
- oxidační stres fyziologie MeSH
- plavání MeSH
- zinek metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- cvičení fyziologie MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- lipolýza genetika MeSH
- mentální anorexie metabolismus MeSH
- techniky in vitro MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kongresy MeSH
