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Abstract
We report the influence of aging on multiple markers of oxidative-nitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36-month) Fischer 344/NNiaHSd × Brown Norway/BiNia (F344/NXBN) rats. Compared to adult (6-month) hearts, indices of oxidative (superoxide anion [O2•−], 4-hydroxy-2-nonenal [4-HNE]) and nitrosative (protein nitrotyrosylation) stress were 34.1 ± 28.1%, 186 ± 28.1% and 94 ± 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r > 0.669; r > 0.710 and P < 0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in transcriptional (NF-κB) activities, signaling (mitogen-activated protein kinases along with Src), apoptotic (Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress.