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Neuronal Nitric Oxide Synthase and Human Vascular Regulation
Open accessAbstract
Vascular blood flow and its distribution among different vascular beds are regulated by changes in microvascular tone. Nitric oxide (NO) plays a key role in the local paracrine regulation of vessel tone both under resting conditions and when blood flow increases in response to agonist stimulation or increased shear stress. The conventional notion that endothelial NO synthase (eNOS)-derived NO is largely responsible for both effects has been challenged by first-in-human studies with a selective inhibitor of neuronal NOS (nNOS), S-methyl-l-thiocitrulline (SMTC). These studies reveal that SMTC causes a reduction in basal blood flow in the normal human forearm and coronary circulations (that is reversed by l-arginine), without affecting the eNOS-mediated vasodilatation elicited by acetylcholine, substance P, or increased shear stress. S-methyl-l-thiocitrulline also inhibits mental stress-induced vasodilatation. These results are consistent with a significant body of experimental studies suggesting that nNOS plays an important role in the local regulation of vessel tone in other species, independent of the effects of nNOS-derived NO in the central nervous system. These emerging data suggest that eNOS and nNOS have distinct roles in the physiologic local regulation of human microvascular tone in vivo and pave the way for further detailed investigation of the relative contribution of nNOS and eNOS in vascular regulation in human disease.
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“NOS3 and NOS1 were found to have distinct roles in regulating microvascular tone [103]”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [103]
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Metadata
- Authors
- Melikian, N., Seddon, M. D., Casadei, B., Chowienczyk, P. J., & Shah, A. M.
- Affiliations
- King's College London (GB)
- University of Oxford (GB)
- Corresponding author
- Shah, Ajay M.
- Venue
- Trends in Cardiovascular Medicine
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 19
- Issue
- 8
- Pages
- 256-262
- ISSN
- 1050-1738 (ISSN-L)
- PMC
- PMC2984617
- OpenAlex
- W2095106948
- Cited by
- 151
- References
- 43
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 5 · 2023: 16 · 2022: 8 · 2021: 4 · 2020: 10 · 2019: 8 · 2018: 5 · 2017: 11 · 2016: 6 · 2015: 11 · 2014: 15 · 2013: 13 · 2012: 15
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Trends in Cardiovascular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- King's College Hospital NHS Foundation Trust
- National Institute for Health and Care Research
- British Heart Foundation (FS/09/062/27958)
- King's College London
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- neuronal nitric oxide synthase, endothelial nitric oxide synthase, nitric oxide, microvascular tone, S-methyl-L-thiocitrulline, L-arginine, shear stress, acetylcholine, substance P, coronary circulation, forearm blood flow, paracrine regulation
- MeSH terms
- Animals, Citrulline, Coronary Vessels, Enzyme Inhibitors, Forearm, Humans, Microcirculation, Nitric Oxide, Stress, Psychological, Thiourea, Vasodilation, Nitric Oxide Synthase Type I, Nitric Oxide Synthase Type III, Microvessels
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