Fat-Diets in Perinatal Stages Altered Nr3c2-Mediated Ca2+ Currents in Mesenteric Arteries of Offspring Rats.

Abstract

Perinatal high-fat diets (PHF) can influence fetal/neonate development, resulting in cardiovascular pathogenesis, but precise mechanisms remain unclear. This study tests aldosterone receptor-mediated Ca2+ influx and the underlying mechanisms influenced by PHF. Maternal S.D. rats receive PHF during pregnancy and lactation periods. Their male offspringare fed normal diets after weaning for four months. Mesenteric arteries (MA)are for electrophysiological testing, Ca2+ imaging, target gene expression, and promotor methylation. PHF increases aldosterone receptor gene Nr3c2-mediated Ca2+ currents in the smooth muscle cells (SMCs) of the MA via L-type Ca2+ channels (LTCC) in the offspring. The increased expression of aldosterone-receptors and LTCCare responsible for an activated Nr3c2-LTCC pathway in the vasculature, eventually predisposes an increase of Ca2+ influx in the myocytes of resistance arteries. The inhibitor of aldosterone-receptors suppresses the increased Ca2+ currents in the SMCs. Nr3c2 and LTCCare upregulated through the transcriptional mechanism in methylation, whichcan be reversed in the functional changes by methylation inhibitor 5AZA. The results firstly demonstrate that aldosterone-receptor activation can stimulate Ca2+ currents via LTCC in vascular myocytes, which can be altered by perinatal foods via epigenetic changes of DNA methylation in the promoters of Nr3c2 and LTCC.