biostudies-literatureKawakami-Mori FJSPS, AMED-CREAST JapanAMED95625https://www.ebi.ac.uk/biostudies/studies/S-EPMC6238751biostudies-literatureUnknown3(21)Maternal malnutrition, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming, leading to hypertension in offspring. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, a synthetic glucocorticoid, mRNA expression of angiotensin receptor type 1a (Agtr1a) in the paraventricular nucleus (PVN) of the hypothalamus was upregulated, concurrent with reduced expression of DNA methyltransferase 3a (Dnmt3a), reduced binding of DNMT3a to the Agtr1a gene, and DNA demethylation. Salt loading increased BP in both types of offspring, suggesting that elevated hypothalamic Agtr1a expression is epigenetically modulated by excessive glucocorticoid and leads to adult-onset salt-sensitive hypertension. Consistent with this, dexamethasone treatmJCI insightAberrant DNA methylation of hypothalamic angiotensin receptor in prenatal programmed hypertension.PMC6238751JP18ek0210093Grant Number 15H05788Ueda KKohno DNishimoto MKawarazaki WFujita TOba SReheman LAyuzawa NKawakami-Mori FHirohama DShimosawa TMarumo TfalseAberrant DNA methylation of hypothalamic angiotensin receptor in prenatal programmed hypertension.Maternal malnutrition, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming, leading to hypertension in offspring. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, a synthetic glucocorticoid, mRNA expression of angiotensin receptor type 1a (Agtr1a) in the paraventricular nucleus (PVN) of the hypothalamus was upregulated, concurrent with reduced expression of DNA methyltransferase 3a (Dnmt3a), reduced binding of DNMT3a to the Agtr1a gene, and DNA demethylation. Salt loading increased BP in both types of offspring, suggesting that elevated hypothalamic Agtr1a expression is epigenetically modulated by excessive glucocorticoid and leads to adult-onset salt-sensitive hypertension. Consistent with this, dexamethasone treatm2018-01-01T00:00:00Z2018 Nov2026-05-06T23:24:43.122Z2019-03-27T00:08:44ZS-EPMC62387513038571110.1172/jci.insight.95625