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

Abstract

Scope: 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.

Methods and results: Maternal S.D. rats receive PHF during pregnancy and lactation periods. Their male offspring are 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 LTCC are 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 LTCC are upregulated through the transcriptional mechanism in methylation, which can be reversed in the functional changes by methylation inhibitor 5AZA.

Conclusion: 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.

Keywords: Nr3c2; calcium currents; methylation; mineralocorticoid receptors; patch clamps.