Deconstructing endothelial dysfunction: soluble guanylyl cyclase oxidation and the NO resistance syndrome
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In this issue of the JCI, Stasch and colleagues suggest that a novel drug, BAY 58-2667, potently activates a pool of oxidized and heme-free soluble guanylyl cyclase (sGC; see the related article beginning on page 2552). The increased vasodilatory potency of BAY 58-2667 the authors found in a number of animal models of endothelial dysfunction and in human blood vessels from patients with diabetes suggests that there exists a subphenotype of endothelial dysfunction characterized by receptor-level NO resistance. Diseases associated with NO resistance would appear to be ideally suited for therapies directed at restoring redox homeostasis, sGC activity, and NO sensitivity.
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The activity of sGC itself is compromised in a number of pathological conditions.
“Apart from changes in NO levels or downstream signaling, the activity of sGC itself is compromised in a number of pathological conditions (355, 363, 600, 853, 888, 1022).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [363]
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- Authors
- Gladwin, M. T.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Gladwin, Mark T.
- ORCID
- Gladwin, Mark T.
- Venue
- Journal of Clinical Investigation
- Published
- 2006-09-01
- Volume
- 116
- Issue
- 9
- Pages
- 2330-2332
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1986547098
- Cited by
- 85
- References
- 22
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 8 · 2022: 1 · 2021: 8 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 3 · 2013: 7 · 2012: 4
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (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, soluble guanylate cyclase, BAY 58-2667, nitric oxide resistance, nitric oxide signaling, redox homeostasis, diabetes mellitus, vasodilation
- MeSH terms
- Soluble Guanylyl Cyclase, Animals, Benzoates, Endothelium, Vascular, Cyclic GMP, Guanylate Cyclase, Humans, Nitric Oxide, Oxidation-Reduction, Vasodilation, Receptors, Cytoplasmic and Nuclear
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