BKCa channel activity and vascular contractility alterations with hypertension and aging via β1 subunit promoter methylation in mesenteric arteries

Hypertension Research : Official Journal of the Japanese Society of Hypertension
Yanyan ZhangLijun Shi

Abstract

Promoter methylation is a key mechanism in the epigenetic reprogramming of gene expression patterns. Here, we investigated the contribution of DNA methylation and the associated expression and function of large-conductance Ca2+-activated K+ (BKCa) channel in mesenteric arteries when hypertension was superimposed on aging. Male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at young (12 weeks), adult (36 weeks) and old (64 weeks) life stages were used. BKCa channel currents, BKCa channel activity in regulating vascular tone, and BKCa channel β1 subunit (BKβ1) function and expression were greater in mesenteric arteries from SHR than from age-matched WKY controls. Consistently, hypertension decreased CpG methylation of the BKβ1 promoter at all ages. Furthermore, aging triggered an increase in BKβ1 promoter methylation in both old WKY and SHR, with concomitant suppression of the β1 subunit and BKCa channel activity. Aging enhanced β1 gene promoter methylation and subunit expression without changing BKCa channel function between young and adult WKY animals. In contrast, aging did not alter CpG methylation but facilitated BKCa channel currents and upregulated BKβ1 expression and function in adult SHR. Taken togethe...Continue Reading

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