Journal article
Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice
American journal of physiology. Heart and circulatory physiology, Vol.293(6), pp.H3726-3731
12/2007
DOI: 10.1152/ajpheart.01116.2007
PMID: 17965276
Abstract
Endotoxin [or lipopolysaccharide (LPS)] increases levels of superoxide in blood vessels and impairs vasomotor function. Angiotensin II plays an important role in the generation of superoxide in several disease states, including hypertension and heart failure. The goal of this study was to determine whether the activation of the renin-angiotensin system contributes to oxidative stress and endothelial dysfunction after endotoxin. We examined the effects of enalapril (an angiotensin-converting enzyme inhibitor) or L-158809 (an angiotensin receptor blocker) on increases of superoxide and vasomotor dysfunction in mice treated with LPS. C57BL/6 mice were treated with either enalapril (60 mg.kg(-1).day(-1)) or L-158809 (30 mg.kg(-1).day(-1)) for 4 days. After the third day, LPS (10-20 mg/kg) or vehicle was injected intraperitoneally, and one day later, vasomotor function of the aorta was examined in vitro. After precontraction with PGF(2alpha), the maximal responses to sodium nitroprusside were similar in the aorta from normal and LPS-treated mice. In contrast, the relaxation to acetylcholine was impaired after LPS (54 +/- 5% at 10(-5), mean +/- SE) compared with vessels treated with vehicle (88 +/- 1%; P < 0.05). Enalapril improved (P < 0.05) relaxation in response to acetylcholine to 81 +/- 6% after LPS. L-158809 also improved relaxation in response to acetylcholine to 77 +/- 4% after LPS. Superoxide (measured with lucigenin and hydroethidine) was increased (P < 0.05) in aorta after LPS, and levels were reduced (P < 0.05) following enalapril and L-158809. Thus, after LPS, enalapril and L-158809 reduce superoxide levels and improve relaxation to acetylcholine in the aorta. The findings suggest that activation of the renin-angiotensin system contributes importantly to oxidative stress and endothelial dysfunction after endotoxin.
Details
- Title: Subtitle
- Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice
- Creators
- Donald D Lund - Department of Internal Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USARobert M BrooksFrank M FaraciDonald D Heistad
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.293(6), pp.H3726-3731
- Publisher
- United States
- DOI
- 10.1152/ajpheart.01116.2007
- PMID
- 17965276
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Grant note
- DK 54759 / NIDDK NIH HHS HL 62984 / NHLBI NIH HHS NS 24621 / NINDS NIH HHS HL 38901 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/2007
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040435102771
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