254 the Role of Renin-Angiotensin System in the Adrenals of Offspring After Exposure to Maternal Dietary Restriction During the Periconceptional Period

Abstract

Abstracts e77ventricle samples were collected from the lambs at d21 for the analysis of gene and protein expression. ResultsThere was increased plasma renin activity and ANGII concentrations in LBW compared to ABW lambs. There was increased ACE2 mRNA and decreased abundance of ATR1 but no changes in abundance of ACE or ATR2 in LBW compared to ABW lambs. There was increased phospho-Akt protein and decreased capillary density in the heart of LBW lambs compared to ABW lambs. There was decreased collagen I and II mRNA expression but no evidence of cardiac remodelling or fi brosis in the LBW lambs. There was decreased FoxO1 and FoxO3a protein in the LBW lambs compared to ABW lambs, but no changes in autophagy proteins: phospho-FoxO1, phospho-FoxO3a, Beclin1, LC3B and LAMP1 was not altered in LBW lambs.Conclusion Although circulating and local cardiac RAS components were altered in LBW lambs there was no increase in fi brosis or autophagy in the heart of the LBW lamb. LBW resulted in decreased capillary density during early postnatal life and this may result in an increased risk of impaired heart function in later life.It has previously been shown that periconceptional dietary restriction in normal and overweight ewes results in increased adrenal weight and cortisol response to stress in postnatal lambs, however the mechanisms underlying these changes are not known. The activation of intraadrenal renin-angiotensin system (RAS) has been demonstrated to promote adrenal growth and steroidogenesis through angiotensin II type I receptor (AT1R) activation.Donor ewes were assigned to one of 4 nutritional treatment groups preconception: CC, 100% metabolisable energy requirement (MER) for 5 months; CR, 100%MER for 4 months followed by 70% MER for 1 month; HH, ad libitum (180% MER) for 5 months; HR, ad libitum for 4 months followed by 70%MER for 1 month. At 6-7 d post-conception, single embryos were transferred into normal weight recipient ewes. Post mortem was conducted and adrenal glands collected from lambs at 4 months of age.In females, there was a signifi cant decrease in adrenal ACE2 mRNA expression in CR and HH than CC by qRT-PCR. ACE and AT1R immunostaining intensity in both the zona glomerulosa (ZG) and zona fasciculata-reticularis (ZF-ZR) of the adrenal cortex was higher in CR and HR than CC. There was no difference in the methylation levels of the AT1R and ACE gene promoter by combined bisulphite restriction assay in the lamb adrenal.These results demonstrate that there is an activation of the intraadrenal RAS, through an increase in ACE and AT1R and a decrease in ACE2, in the adrenal cortex of offspring exposed to dietary restriction during the periconceptional period.Background Elevated blood pressure (BP) in children and adolescents increases future risk of cardiovascular disease. The study aimed to identify the prevalence of elevated BP and risk factors among children aged 3 to 18 years from Beijing.