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We investigated whether hypertension induced by maternal lipopolysaccharide (LPS) administration during gestation is linked to peripheral vascular and renal hemodynamic regulation, through angiotensin II → NADPH-oxidase signalling, and whether these changes are directly linked to intrauterine oxidative stress. Female Wistar rats were submitted to LPS, in the absence or presence of α-tocopherol during pregnancy. Malondialdehyde in placenta and in livers from dams and foetuses was enhanced by LPS. Tail-cuff systolic blood pressure (tcSBP) was elevated in the 16-week-old LPS offspring. Renal malondialdeyde and protein expression of NADPH oxidase isoform 2 were elevated in these animals at 20 weeks of age. Maternal α-tocopherol treatment prevented the elevation in malondialdehyde induced by LPS on placenta and livers from dams and foetuses, as well as prevented the elevation in tcSBP and the elevation in renal malondialdehyde in adult life. LPS offspring presented impairment of endothelium-dependent relaxation in aorta and mesenteric rings, which was blunted by angiotensin type 1 receptor (AT 1 R) blockade and NADPH oxidase inhibition. At age of 32 weeks, renal hemodynamic parameters were unchanged in anaesthetised LPS offspring, but angiotensin II infusion led to an increased glomerular filtration rate paralleled by filtration fraction elevation. The renal haemodynamic changes provoked by angiotensin II was prevented by early treatment with α-tocopherol and by late treatment with NADPH oxidase inhibitor. These results point to oxidative stress as a mediator of offspring hypertension programmed by maternal inflammation and to the angiotensin II → NADPH oxidase signalling pathway as accountable for vascular and renal dysfunctions that starts and maintains hypertension., (Copyright © 2018. Published by Elsevier B.V.)

α-Tocopherol (α-Toc) overload increases the risk of dying in humans (E.R. Miller III et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality Ann Int Med. 142 (2005) 37-46), and overload during early development leads to elevation of blood pressure at adult life, but the mechanism(s) remains unknown. We hypothesized that α-Toc overload during organogenesis affects the renal renin angiotensin system (RAS) components and renal Na + handling, culminating with late elevated blood pressure. Pregnant Wistar rats received α-Toc or the superoxide dismutase mimetic tempol throughout pregnancy. We evaluated components of the intrarenal renin angiotensin system in neonate and juvenile offspring: Ang II-positive cells, Ang II receptors (AT 1 and AT 2 ), linked protein kinases, O 2 - production, NADPH oxidase abundance, lipid peroxidation and activity of Na + -transporting ATPases. In juvenile offspring we followed the evolution of arterial blood pressure. Neonates from α-Toc and tempol mothers presented with accentuated retardment in tubular development, pronounced decrease in glomerular Ang II-positive cells and AT 1 /AT 2 ratio, intense production of O 2 - and upregulation of the α, ε and λ PKC isoforms. α-Toc decreased or augmented the abundance of renal (Na + +K + )ATPase depending on the age and α-Toc dose. In juvenile rats the number of Ang II-positive cells returned to control values as well as PKCα, but co-existing with marked upregulation in the activity of (Na + +K + ) and Na + -ATPase and elevated arterial pressure at 30 days. We conclude that the mechanisms of these alterations rely on selective targeting of renal RAS components through genic and pro-oxidant effects of the vitamin., (Copyright © 2018 Elsevier B.V. All rights reserved.)