Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension
Abstract
Endothelial dysfunction in the setting of cardiovascular risk factors such as hypercholesterolemia, diabetes mellitus, chronic smoking, as well hypertension, is, at least in part, dependent of the production of reactive oxygen species (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide (NO). ROS-producing enzymes involved in increased oxidative stress within vascular tissue include NADPH oxidase, xanthine oxidase, and mitochondrial superoxide producing enzymes. Superoxide produced by the NADPH oxidase may react with NO, thereby stimulating the production of the NO/superoxide reaction product peroxynitrite. Peroxynitrite in turn has been shown to uncouple eNOS, therefore switching an antiatherosclerotic NO producing enzyme to an enzyme that may accelerate the atherosclerotic process by producing superoxide. Increased oxidative stress in the vasculature, however, is not restricted to the endothelium and also occurs within the smooth muscle cell layer. Increased superoxide production has important consequences with respect to signaling by the soluble guanylate cyclase and the cGMP-dependent kinase I, which activity and expression is regulated in a redox-sensitive fashion. The present review will summarize current concepts concerning eNOS uncoupling, with special focus on the role of tetrahydrobiopterin in mediating eNOS uncoupling.
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Increased vascular oxidative stress decreases NO bioavailability and contributes to the formation of peroxynitrite, a highly oxidant molecule.
“which decreases NO bioavailability and also contributes to the formation of peroxynitrite, a highly oxidant molecule [32].”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [32]
Both xanthine oxidase and NADPH oxidase have been implicated as important prooxidant enzymes contributing to hypertension.
“Both enzymes have been implicated as important prooxidant enzymes contributing to hypertension [32,50,51].”
From Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension (2011) · cites this paper as [32]
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A Novel Paradigm for Heart Failure With Preserved Ejection Fraction
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The Science of Stroke: Mechanisms in Search of Treatments
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Montenegro, M. F., Amaral, J. H., Pinheiro, L. C., Sakamoto, E. K., Ferreira, G. C., Reis, R. I., Marçal, D. M. O., Pereira, R. P., & Tanus-Santos, J. E. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.005 · Cited by 152 · see citing works
Nox1, 2, 4, 5: Counting out oxidative stress
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Redox implications in adipose tissue (dys)function-A new look at old acquaintances
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Quercetin restores plasma nitrite and nitroso species levels in renovascular hypertension
Montenegro, M. F., Neto-Neves, E. M., Dias-Junior, C. A., Ceron, C. S., Castro, M. M., Gomes, V. A., Kanashiro, A., & Tanus-Santos, J. E. (2010) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-010-0546-1 · Cited by 52 · see citing works
- Authors
- Schulz, E., Jansen, T., Wenzel, P., Daiber, A., & Münzel, T.
- Affiliations
- II. Medizinische Klinik, Mainz, Kardiologie, Angiologie und Internistische Intensivmedizin, Mainz, Germany.
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2008-06
- Volume
- 10
- Issue
- 6
- Pages
- 1115-1126
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- OpenAlex
- W1975365056
- Cited by
- 430
- References
- 96
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 18 · 2023: 11 · 2022: 15 · 2021: 21 · 2020: 22 · 2019: 18 · 2018: 17 · 2017: 12 · 2016: 22 · 2015: 30 · 2014: 27 · 2013: 35 · 2012: 37
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Antioxidants and Redox Signaling (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- endothelial dysfunction, hypertension, nitric oxide, tetrahydrobiopterin, oxidative stress, reactive oxygen species, superoxide, NADPH oxidase, xanthine oxidase, peroxynitrite, eNOS uncoupling, soluble guanylate cyclase, vascular smooth muscle cells, atherosclerosis
- MeSH terms
- Soluble Guanylyl Cyclase, Animals, Biopterins, Endothelium, Vascular, Guanylate Cyclase, Humans, Hypertension, Nitric Oxide, Cyclic GMP-Dependent Protein Kinases, Receptors, Cytoplasmic and Nuclear, Oxidative Stress, NADPH Oxidases, Peroxynitrous Acid, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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