p22phox mRNA Expression and NADPH Oxidase Activity Are Increased in Aortas From Hypertensive Rats
Abstract
Recent studies suggest that superoxide production by the NADPH/NADH oxidase may be involved in smooth muscle cell growth and the pathogenesis of hypertension. We previously showed that angiotensin II (Ang II) activates a p22phox-based NADPH/NADH oxidase in cultured rat vascular smooth muscle cells and in animals made hypertensive by infusion of Ang II. To investigate the mechanism responsible for this increased oxidase activity, we examined p22phox mRNA expression in rats made hypertensive by implanting an osmotic minipump that delivered Ang II (0.7 mg/kg per day). Blood pressure began to increase 3 days after the start of Ang II infusion and remained elevated for up to 14 days. Expression of p22phox mRNA in aorta was also increased after 3 days and reached a maximum increase of 338±41% by 5 days after pump implantation compared with the value after sham operation. This increase in mRNA expression was accompanied by an increase in the content of the corresponding cytochrome (twofold) and NADPH oxidase activity (179±11% of that in sham-operated rats 5 days after pump implantation). Treatment with the antihypertensive agents losartan (25 mg/kg per day) or hydralazine (15 mg/kg per day) inhibited this upregulation of mRNA levels and activity. Furthermore, infusion of recombinant heparin-binding superoxide dismutase decreased both blood pressure and p22phox mRNA expression. In situ hybridization of aortic tissue showed that p22phox mRNA was expressed in medial smooth muscle as well as in the adventitia. These findings suggest that Ang II–induced hypertension activates the NADPH/NADH oxidase system by upregulating mRNA levels of one or several components of this oxidase system, including the p22phox, and that the NADPH/NADH oxidase system is associated with the pathology of hypertension in vivo.
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In response to increased levels of ROS, PKC is activated, which in turn can activate NOXs.
“In response to the increased levels of ROS, the PKC is activated, which in turn, can activate NOXs (319, 776).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [319]
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- Authors
- Fukui, T., Ishizaka, N., Rajagopalan, S., Laursen, J. B., Capers, Q., Taylor, W. R., Harrison, D. G., de Leon, H., Wilcox, J. N., & Griendling, K. K.
- Affiliations
- Emory University (US)
- the Department of Medicine, Divisions of Cardiology (T.F., N.I., S.R., J.B.L., Q.C. IV, W.R.T., D.G.H., K.K.G.) and Hematology/Oncology (H. de L., J.N.W.), Emory University; The Atlanta Veteran's Affairs Medical Center (W.R.T., D.G.H.), Atlanta, Ga; and Medical Department B (J.B.L.), National University Hospital, Rigshospitalet, Copenhagen, Denmark.
- ORCID
- Venue
- Circulation Research
- Published
- 1997-01
- Volume
- 80
- Issue
- 1
- Pages
- 45-51
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W1998830072
- Cited by
- 553
- References
- 25
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 7 · 2021: 1 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 15 · 2016: 10 · 2015: 16 · 2014: 19 · 2013: 11 · 2012: 22
- FWCI
- 16.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL38206)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- p22phox, NADPH oxidase, angiotensin II, hypertension, aorta, superoxide production, vascular smooth muscle cells, losartan, hydralazine, mRNA expression, cytochrome b5, blood pressure
- MeSH terms
- Angiotensin II, Animals, Antihypertensive Agents, Aorta, Biphenyl Compounds, Blood Pressure, Diabetes Mellitus, Experimental, Hydralazine, Imidazoles, Male, NADPH Dehydrogenase, Phosphoproteins, RNA, Messenger, Superoxide Dismutase, Systole, Tetrazoles, Rats, Sprague-Dawley, In Situ Hybridization, NADPH Oxidases, Losartan, Membrane Transport Proteins, Rats
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