Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery

Cannon, Richard O.; Schechter, Alan N.; Panza, Julio A.; Ognibene, Frederick P.; Pease-Fye, Margaret E.; Waclawiw, Myron A.; Shelhamer, James H.; Gladwin, Mark T.

doi:10.1172/jci200112761

Cited by 298Nitric Oxide and Endothelin EffectsCardiovascular Health and Disease PreventionHemoglobin structure and function

Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery

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Cannon, Richard O., Schechter, Alan N., Panza, Julio A., Ognibene, Frederick P., Pease-Fye, Margaret E., Waclawiw, Myron A., Shelhamer, James H., Gladwin, Mark T.·2001·Journal of Clinical Investigation

DOI 10.1172/jci200112761PMC PMC203029

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Abstract

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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Infusion of a competitive inhibitor of eNOS into the human systemic or coronary circulation decreases basal blood flow by approximately 25%.
“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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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.
ORCID: Schechter, Alan N.
Panza, Julio A.
Gladwin, Mark T.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2001-07-15
Volume: 108
Issue: 2
Pages: 279-287
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci200112761
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 › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › 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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Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxidedelivery

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