Abstract:
BACKGROUND:The mechanisms by which heme oxygenase (HO) improves glucose metabolism in essential hypertension are not completely understood. Because dysfunctional insulin signaling is associated with elevated inflammation and high cholesterol and triglycerides, we investigated the effects of HO on the proinflammatory macrophage M1 phenotype and the anti-inflammatory macrophage M2 phenotype in spontaneously hypertensive rats (SHRs). SHRs are a model of human essential hypertension with features of metabolic syndrome, including impaired glucose metabolism. METHODS:Spectrophotometric analysis, enzyme immunoassay, enzyme-linked immunosorbent assay, and Western immunoblotting were used. HO was enhanced with hemin or inhibited with chromium-mesoporphyrin (CrMP). RESULTS:Hemin suppressed inflammation by abating proinflammatory macro phage M1 phenotype (ED1) and chemokines such as macrophage chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein 1 alpha (MIP-1α) while enhancing anti-inflammatory macrophage M2 phenotype by potentiating ED2, CD206, and CD14. Similarly, hemin improved insulin signaling by enhancing insulin receptor substrate 1 (IRS-1), IRS-2, phosphatidylinositol 3 kinase (PI3K), and glucose transporter 4 (GLUT4) but reduced total cholesterol and triglycerides. These effects were accompanied by increased HO-1, HO activity, and cyclic guanosine monophosphate (cGMP), whereas the HO inhibitor CrMP nullified the hemin effects. Importantly, the effects of the HO system on ED1, ED2, CD206, and CD14 in SHRs are novel. CONCLUSIONS:Hemin abated inflammation in SHRs by selectively enhancing the anti-inflammatory macrophage M2 phenotype that dampens inflammation while suppressing the pronflammatory macrophage M1 phenotype and related chemokines such as MCP-1 and MIP-1α. Importantly, the reduction of inflammation, total cholesterol, and triglycerides was accompanied by the enhancement of important proteins implicated in insulin signaling, including IRS-1, IRS-2, PI3K, and GLUT4. Thus, the concomitant reduction of inflammation, total cholesterol and triglycerides and the corresponding potentiation of insulin signaling are among the multifaceted mechanisms by which the HO system improves glucose metabolism in essential hypertension.
journal_name
Am J Hypertensjournal_title
American journal of hypertensionauthors
Ndisang JF,Mishra Mdoi
10.1093/ajh/hpt082subject
Has Abstractpub_date
2013-09-01 00:00:00pages
1123-31issue
9eissn
0895-7061issn
1941-7225pii
hpt082journal_volume
26pub_type
杂志文章abstract:BACKGROUND:Beetroot has attracted much attention because of its blood pressure-lowering properties. Although beetroot contains various nutritional compounds, including inorganic nitrate, some of their physiological properties are not fully understood. In this study, we examined whether betanin, a beetroot component, ha...
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更新日期:1991-09-01 00:00:00
abstract:BACKGROUND:Left atrial (LA) dilatation is associated with unfavorable outcome in hypertension. However, there are few data on clinical, demographic, and echocardiographic findings correlated with LA dilatation development. METHODS:From the Campania-Salute Network registry, we identified 5,375 hypertensive patients (52...
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/3.8.210
更新日期:1990-08-01 00:00:00
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journal_title:American journal of hypertension
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journal_title:American journal of hypertension
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doi:10.1016/s0895-7061(99)00027-8
更新日期:1999-05-01 00:00:00
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doi:10.1016/j.amjhyper.2005.01.014
更新日期:2005-07-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2004.11.031
更新日期:2005-05-01 00:00:00
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更新日期:2014-11-01 00:00:00
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journal_title:American journal of hypertension
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doi:10.1016/j.amjhyper.2007.01.014
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journal_title:American journal of hypertension
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abstract::The aim of this study was to compare the efficacy (lowering diastolic blood pressure to 90 mm Hg or less) of urapidil, a postsynaptic alpha-blocker with central action with that of captopril in a randomized, double-blind, multicenter study. Two hundred ninety-five essential hypertensives (WHO I/II) (140 male, 155 fema...
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:1988-07-01 00:00:00
abstract::The effects of increased dietary calcium intake on blood pressure and arterial function were investigated in one-kidney deoxycorticosterone-salt hypertensive Wistar rats. The calcium content of the control diet was 1.1%, and that of the high calcium diet, 2.5%. During the 10-week study calcium supplementation markedly...
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pub_type: 杂志文章,meta分析
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更新日期:2005-07-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2008.157
更新日期:2008-06-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章,评审
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更新日期:2000-05-01 00:00:00
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journal_title:American journal of hypertension
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doi:10.1093/ajh/hpx189
更新日期:2018-03-10 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2009.101
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journal_title:American journal of hypertension
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doi:10.1093/ajh/7.11.948
更新日期:1994-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:1990-02-01 00:00:00
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journal_title:American journal of hypertension
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doi:10.1016/j.amjhyper.2005.03.747
更新日期:2005-09-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2006.06.012
更新日期:2007-01-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.amjhyper.2004.12.022
更新日期:2005-06-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章,评审
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更新日期:2011-09-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2013-07-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/2.2.78
更新日期:1989-02-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2008-03-01 00:00:00