Abstract:
BACKGROUND:The expression of Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) is upregulated in spontaneously hypertensive rat (SHR). We investigated whether expression of NKCC1 is epigenetically regulated during postnatal development of hypertension. METHODS:The mesenteric arteries from 5-, 10-, and 18-week-old Wistar-Kyoto rats (WKY) and SHRs were subjected to vascular contraction. We determined expression levels of Nkcc1 mRNA and protein, methylation status, and histone modification of Nkcc1 promoter, and DNA methyltransferase (DNMT) activity. RESULTS:The inhibition of dose-response curves by bumetanide, an inhibitor of NKCC1, as well as the expression of Nkcc1 mRNA and protein was comparable between 5-week-old SHR and age-matched WKY, but greater in 18-week-old SHR than in age-matched WKY. Nkcc1 promoter in WKY was getting methylated with age whereas that in SHR mostly remained hypomethylated after development of hypertension. DNMT3B was highly associated with the promoter of WKY, whereas the CXXC finger protein 1 (Cfp1) was highly bound to the promoter of SHR. At the age of 18 weeks, the DNMT activity in aorta of WKY was about threefold higher than that of SHR. The transcription-activating histone code acetyl H3 was higher in SHR than in WKY, whereas suppressive histone code dimethyl H3K9 was greater in WKY than in SHR. CONCLUSION:It is concluded that expression of NKCC1 is epigenetically upregulated during postnatal development of hypertension. Our data indicate that maintenance of hypomethylation in Nkcc1 promoter of SHR resulting from low DNMT activity plays an important role in the upregulation of NKCC1 during development of spontaneous hypertension.
journal_name
Am J Hypertensjournal_title
American journal of hypertensionauthors
Cho HM,Lee HA,Kim HY,Han HS,Kim IKdoi
10.1038/ajh.2011.136subject
Has Abstractpub_date
2011-12-01 00:00:00pages
1286-93issue
12eissn
0895-7061issn
1941-7225pii
ajh2011136journal_volume
24pub_type
杂志文章abstract::Ca2+ efflux from cultured vascular smooth muscle cells (VSMC) consists of two mechanisms: one is dependent on extracellular sodium, mediated by the Na(+)-Ca2+ exchange (Na+o-dependent Ca2+ efflux), and the other is independent of extracellular sodium but is mediated by the Ca(2+)-pump (Na+o-independent Ca2+ efflux). I...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/7.7.597
更新日期:1994-07-01 00:00:00
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更新日期:2005-02-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2007.3
更新日期:2008-01-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
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更新日期:2007-08-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1093/ajh/1.1.91
更新日期:1988-01-01 00:00:00
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journal_title:American journal of hypertension
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更新日期:2001-01-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
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更新日期:2020-07-18 00:00:00
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更新日期:2017-02-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(98)00256-8
更新日期:1999-04-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/4.3.234
更新日期:1991-03-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2011.175
更新日期:2012-01-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/5.9.616
更新日期:1992-09-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
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更新日期:2020-03-13 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.amjhyper.2005.07.022
更新日期:2006-02-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1038/ajh.2007.62
更新日期:2008-03-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hps100
更新日期:2013-05-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/0895-7061(95)00048-T
更新日期:1995-06-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,随机对照试验
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更新日期:2010-08-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2010-06-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章,多中心研究
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更新日期:2015-05-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1999-10-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/j.amjhyper.2003.09.014
更新日期:2004-02-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
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更新日期:1991-03-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/6.7.593
更新日期:1993-07-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/0895-7061(94)00208-s
更新日期:1995-04-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpu059
更新日期:2014-11-01 00:00:00
abstract:BACKGROUND:Adiposity measures are associated with increased pediatric blood pressure (BP). However, this correlation can be confounded by the relationship of both variables to height. We evaluated whether adiposity and anthropometric measures were associated with pediatric BP before and after adjusting each value for h...
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pub_type: 杂志文章
doi:10.1038/ajh.2010.82
更新日期:2010-08-01 00:00:00