Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction
Open accessAbstract
Background. The gas nitric oxide (NO) is an important endothelium-derived relaxing factor, inactivated by rapid combination with heme in hemoglobin. Methods and Results. Awake spontaneously breathing lambs inhaled 5-80 ppm NO with an acutely constricted pulmonary circulation due to either infusion of the stable thromboxane endoperoxide analogue U46619 or breathing a hypoxic gas mixture. Within 3 minutes after adding 40 ppm NO or more to inspired gas, pulmonary hypertension was reversed. Systemic vasodilation did not occur. Pulmonary hypertension resumed within 3-6 minutes of ceasing NO inhalation. During U46619 infusion pulmonary vasodilation was maintained up to 1 hour without tolerance. In the normal lamb, NO inhalation produced no hemodynamic changes. Breathing 80 ppm NO for 3 hours did not increase either methemoglobin or extravascular lung water levels nor modify lung histology compared with control lambs. Conclusions. Low dose inhaled NO (5-80 ppm) is a selective pulmonary vasodilator reversing both hypoxia- and thromboxane-induced pulmonary hypertension in the awake lamb [corrected].
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Inhaled NO induces vasodilation in PAH and is capable of reversing hypoxic pulmonary vasoconstriction.
“Inhaled NO induces vasodilation in PAH and is capable of reversing hypoxic pulmonary vasoconstriction[139–141].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [139]
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- Authors
- Frostell, C., Fratacci, M. D., Wain, J. C., Jones, R., & Zapol, W. M.
- Affiliations
- Harvard University (US)
- Venue
- Circulation
- Published
- 1991-06
- Volume
- 83
- Issue
- 6
- Pages
- 2038-2047
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1927797304
- Cited by
- 1,128
- References
- 42
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 20 · 2023: 14 · 2022: 20 · 2021: 16 · 2020: 20 · 2019: 17 · 2018: 16 · 2017: 26 · 2016: 19 · 2015: 21 · 2014: 11 · 2013: 12 · 2012: 20
- FWCI
- 80.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-42397, R01HL042397)
- Fogarty International Center
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- inhaled nitric oxide, pulmonary vasodilation, hypoxic pulmonary vasoconstriction, pulmonary hypertension, thromboxane, U46619, endothelium-derived relaxing factor, hemoglobin, methemoglobin, extravascular lung water, lambs
- MeSH terms
- Administration, Inhalation, Animals, Hypoxia, Dose-Response Relationship, Drug, Drug Tolerance, Infusions, Intravenous, Nitric Oxide, Prostaglandin Endoperoxides, Synthetic, Pulmonary Circulation, Sheep, Time Factors, Vasoconstriction, Vasodilator Agents
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