Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans

• Published in: Journal of molecular and cellular cardiology 2011-04, Vol.50 (4), p.686-694
• Main Authors: Konior, Anna, Klemenska, Emilia, Brudek, Magdalena, Podolecka, Ewa, Czarnowska, Elżbieta, Beręsewicz, Andrzej
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Cardiovascular; Dinoprost - analogs & derivatives; Dinoprost - metabolism; Endothelial NO synthase; Endothelium, Vascular - metabolism; Female; Glycocalyx - metabolism; Guinea Pigs; Heart - physiology; Humans; Male; NADPH oxidase; NADPH Oxidases - metabolism; Oxidative stress; Oxidative Stress - physiology; Rats; Rats, Wistar; Seasonality; Seasons; Superoxide dismutase; Superoxides - metabolism; Vasodilation - physiology; Xanthine oxidase; Xanthine Oxidase - metabolism
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/j.yjmcc.2010.11.010

Abstract 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 (O2− ) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O2− overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O2− -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 O2− , 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 O2− -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 O2− -overproduction.