Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans.
Seasonality in endothelial dysfunction and oxidative stress was noted in humans and rats, suggesting it is a common phenomenon of a potential clinical relevance. We aimed at studying (i) seasonal variations in cardiac superoxide (O(2)(-)) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O(2)(-) overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O(2)(-)-overproduction is associated with a pro-inflammatory endothelial activation, and (iv) how the summer-associated changes compare to those caused by diabetes, a classical cardiovascular risk factor. Langendorff-perfused guinea-pig and rat hearts generated ~100% more O(2)(-), and human subjects excreted 65% more 8-isoprostane in the summer vs. other seasons. Inhibitors of NADPH oxidase, xanthine oxidase, and NO synthase inhibited the seasonal O(2)(-)-overproduction. In the summer vs. other seasons, cardiac NADPH oxidase and xanthine oxidase activity, and protein expression were increased, the endothelial NO synthase and superoxide dismutases were downregulated, and, in guinea-pig hearts, adhesion molecules upregulation and the endothelial glycocalyx destruction associated these changes. In guinea-pig hearts, the summer and a streptozotocin-induced diabetes mediated similar changes, yet, more severe endothelial activation associated the diabetes. These findings suggest that the seasonal oxidative stress is a common phenomenon, associated, at least in guinea-pigs, with the endothelial activation. Nonetheless, its biological meaning (regulatory vs. deleterious) remains unclear. Upregulated NADPH oxidase and xanthine oxidase and uncoupled NO synthase are the sources of the seasonal O(2)(-)-overproduction.
Department of Clinical Physiology, Medical Centre of Postgraduate Education, Warsaw, Poland.
Anna
A
Konior
Emilia
E
Klemenska
Magdalena
M
Brudek
Ewa
E
Podolecka
Elżbieta
E
Czarnowska
Andrzej
A
Beręsewicz
D000818:Animals; D015153:Blotting, Western; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D019276:Glycocalyx / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006801:Humans; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012621:Seasons; D013481:Superoxides / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology; D014969:Xanthine Oxidase / Q000378:metabolism
D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D014969:Xanthine Oxidase; D019255:NADPH Oxidases