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Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery
Open accessAbstract
Nitric oxide (NO) may be stabilized by binding to hemoglobin, by nitrosating thiol-containing plasma molecules, or by conversion to nitrite, all reactions potentially preserving its bioactivity in blood.Here we examined the contribution of blood-transported NO to regional vascular tone in humans before and during NO inhalation.While breathing room air and then room air with NO at 80 parts per million, forearm blood flow was measured in 16 subjects at rest and after blockade of forearm NO synthesis with N G -monomethyl-L-arginine (L-NMMA) followed by forearm exercise stress.L-NMMA reduced blood flow by 25% and increased resistance by 50%, an effect that was blocked by NO inhalation.With NO inhalation, resistance was significantly lower during L-NMMA infusion, both at rest and during repetitive hand-grip exercise.S-nitrosohemoglobin and plasma S-nitrosothiols did not change with NO inhalation.Arterial nitrite levels increased by 11% and arterial nitrosyl(heme)hemoglobin levels increased tenfold to the micromolar range, and both measures were consistently higher in the arterial than in venous blood.S-nitrosohemoglobin levels were in the nanomolar range, with no significant artery-to-vein gradients.These results indicate that inhaled NO during blockade of regional NO synthesis can supply intravascular NO to maintain normal vascular function.This effect may have application for the treatment of diseases characterized by endothelial dysfunction.
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“For example, the infusion of a competitive inhibitor of eNOS into the human systemic or coronary circulation decreases basal blood flow by ~25%”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [146]
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Metadata
- Authors
- Cannon, R. O., Schechter, A. N., Panza, J. A., Ognibene, F. P., Pease-Fye, M. E., Waclawiw, M. A., Shelhamer, J. H., & Gladwin, M. T.
- Affiliations
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- National Heart, Lung, and Blood Institute (US)
- Corresponding author
- Cannon, Richard O.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-07-15
- Volume
- 108
- Issue
- 2
- Pages
- 279-287
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC203029
- OpenAlex
- W2161221991
- Cited by
- 298
- References
- 53
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 10 · 2016: 5 · 2015: 16 · 2014: 15 · 2013: 11 · 2012: 13
- FWCI
- 12.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- inhaled nitric oxide, regional blood flow, forearm blood flow, nitric oxide delivery, nitric oxide production, L-NMMA, nitric oxide synthase inhibition, vascular tone, nitrite, S-nitrosohemoglobin, S-nitrosothiols, endothelial dysfunction, handgrip exercise, vascular resistance
- MeSH terms
- Administration, Inhalation, Adult, Biological Transport, Endothelium, Vascular, Female, Forearm, Hemoglobins, Humans, Male, Mercaptoethanol, Middle Aged, Models, Chemical, Nitric Oxide, Nitrites, Nitroso Compounds, Regional Blood Flow, S-Nitrosothiols
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