Abstract P146: Transient Neonatal High Oxygen Exposure Accelerates Adult Cardiac Baseline and Ang Ii-induced Prooxidative and Proinflammatory Responses

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Objective: Preterm birth is associated with disequilibrated early life oxidant-antioxidant and proinflammatory conditions that can be carried into adulthood and contribute to the development of organ dysfunction. Neonatally high O 2 -exposed rats, a model of prematurity-related prooxidative conditions, exhibit adult hypertension, early cardiac dysfunction and fibrosis, and premature angiotensin (ANG) II-induced heart failure. We hypothesized that neonatal high O 2 exposure will exaggerate baseline and ANG II-induced cardiac prooxidative and proinflammatory gene expression in adult rats. Design and Methods: Sprague-Dawley pups were kept in 80% O 2 (H group) or room air (NNI group) from day 3-10 of life. Twelve-weeks-old H and NNI rats were infused with ANG II (100 ng.kg -1 .min -1 ) or saline (NaCl) for 4 weeks (n = 4 per group). RNA extracted from hearts was used in arrays to assess expression of oxidative stress and inflammatory genes. Data is expressed as fold change (F.C.) compared to control NNI+NaCl. Results: H+NaCl exhibited increased baseline Cd68 expression (F.C: 1.47; P<0.05 vs control), tendancy of increased Nfkb1 and Tnf expression (1.52 and 1.48), and a tendancy of decreased Il1b and Il18 expression (0.72 and 0.78). H+ANGII versus NNI+ANGII exhibited similar increase in Tnf ( 2.12 vs 2.13; P<0.05 vs control), greater increase in Cd14 , Cd68 , and Nfkb1 (2.5 vs 1.78, 2.13 vs 1.94, 2.0 vs 1.7; P<0.05 vs controls), and a greater tendancy of increase in Tgfb1 , Myd88 , Cybb , and Gstp1 (2.68 vs 1.82, 2.37 vs 1.31, 1.91 vs 0.98, 2.45 vs 1.61) expression. NNI+ANGII versus H+ANGII exhibited greater increase in expression of genes involved in early inflammatory process, including Ccl2 , Icam1 , and Vcam1 (2.07 vs 1.56, 1.88 vs 1.36, 2.34 vs 1.29; P<0.05 vs control). Conclusions: Neonatal high O 2 exposure accelerates baseline and ANG II-induced cardiac prooxidative and proinflammatory responses in adult rats, which could account for early cardiac abnormalities and premature ANG II-induced heart failure in this model.