Angiotensin II type 1 receptor-mediated peroxide production in human macrophages
Abstract
Our previous experiments demonstrated upregulation of the renin-angiotensin system in macrophages, including angiotensin II type 1 (AT1) and type 2 (AT2) receptors, during transformation from monocytes. We investigated the role of angiotensin II in oxidative stress of monocytes/macrophages, which plays a role in the advance of atherosclerosis. THP1, a human monocytic leukemia cell line, was differentiated to macrophages by adding of phorbol 12-myristate 13-acetate for 24 hours. The intracellular production of peroxide was measured by a cytofluorometric assay with 2', 7'-dichlorofluorescein-diacetate with a flow cytometer scan. Peroxide was detected in monocytes and upregulated during the transformation to macrophages by 3.18+/-0.52 times in relative fluorescein of peak value (P<0.01). Angiotensin II (1 micromol/L) induced oxidative stress in macrophages, with the peak at 15 minutes by 451+/-223%, and returned to the control level within 1 hour. EC50 was 5.4x10(-9) mol/L. AT1 antagonist (CV11974, 1 micromol/L) significantly decreased angiotensin II-induced oxidative stress in macrophages, but AT2 antagonist (PD123319, 1 micromol/L) did not. Of interest, AT1 antagonist also decreased basal levels of peroxide production in macrophages in a dose-dependent manner. These results suggest that upregulation of the expression of AT1 receptor in macrophages contributes in part to upregulation of peroxide production. AT1 receptor antagonists may be useful to suppress oxidative stress of macrophages in atherosclerotic lesions.
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PVMs express AT1 receptors and can produce large amounts of ROS through NOX2.
“As macrophages, PVMs express AT1Rs and have the potential to produce large amounts of ROS through NOX2 (23,24).”
From Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension (2016) · cites this paper as [24]
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References 37 · Cited by 118
Research works printed but not linked: 2
- MERCATOR-Study-Group. Does the new angiotensin converting enzyme inhibitor cilazapril prevent restenosis after percutaneous trans- luminal coronary angioplasty? Results of the MERCATOR study: a multicenter, randomized, double-blind placebo-controlled trial. Circu- lation. 1992;86:100 -110.
- Dzau VJ. Local expression and pathophysiological role of renin-angio- tensin in the blood vessels and heart. Basic Res Cardiol. 1993;1:1-14.
- Authors
- Yanagitani, Y., Rakugi, H., Okamura, A., Moriguchi, K., Takiuchi, S., Ohishi, M., Suzuki, K., Higaki, J., & Ogihara, T.
- Affiliations
- The University of Osaka (JP)
- Venue
- Hypertension
- Published
- 1999-01
- Volume
- 33
- Issue
- 1
- Pages
- 335-339
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2050991399
- Cited by
- 118
- References
- 37
- Citations by year
- 2024: 3 · 2023: 1 · 2021: 4 · 2020: 3 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- angiotensin II type 1 receptor, angiotensin II type 2 receptor, macrophages, oxidative stress, reactive oxygen species, peroxide formation, renin-angiotensin system, monocyte-to-macrophage differentiation, atherosclerosis, angiotensin II, AT1 receptor antagonists, PD123319, THP-1 cells
- MeSH terms
- Angiotensin II, Benzimidazoles, Biphenyl Compounds, Cell Differentiation, Humans, Imidazoles, Kinetics, Leukemia, Monocytic, Acute, Macrophages, Peroxides, Pyridines, Receptors, Angiotensin, Tetradecanoylphorbol Acetate, Tetrazoles, Tumor Cells, Cultured, Oxidative Stress, Receptor, Angiotensin, Type 2, Receptor, Angiotensin, Type 1, Angiotensin Receptor Antagonists
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