High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy
Abstract
Lack of vasodilator substances, such as nitric oxide (NO), has been implicated in the development of pulmonary hypertension, but the pathogenesis of the disease remains speculative. We hypothesized that NO plays a role in the pathogenesis of primary pulmonary hypertension (PPH), and may serve as a sensitive and specific marker of disease progression and/or severity. To test this, exhaled NO and pulmonary artery pressure were measured in individuals with PPH and secondary pulmonary hypertension (SPH) on various therapies, including the potent vasodilator epoprostenol (prostacyclin), compared with healthy controls. NO in exhaled breath of individuals with PPH was lower than SPH or control (p<0.05). In contrast, exhaled NO of individuals with PPH or SPH receiving epoprostenol was strikingly higher than PPH or SPH individuals not receiving epoprostenol, or controls. Concomitant with higher NO levels, right ventricular systolic pressure of individuals significantly decreased with epoprostenol. Importantly, in paired measures of exhaled NO before and after epoprostenol, NO increased in all pulmonary hypertensive individuals 24 h after initiation of epoprostenol therapy (p<0.05). NO may be a useful noninvasive marker of pulmonary hypertension severity and response to prostacyclin therapy.
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The hallmark feature of PAH and other forms of PH is reduced bioavailability of NO signaling and poor endothelial responsiveness to triggers of vasodilatation.
“The hallmark feature of PAH and other forms of PH is reduced bioavailability of NO signaling and poor endothelial responsiveness to triggers of vasodilatation[28–34].”
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 [30]
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- Authors
- özkan, M., Dweik, R. A., Laskowski, D., Arroliga, A. C., & Erzurum, S. C.
- Affiliations
- Cleveland Clinic (US)
- Venue
- Lung
- Published
- 2001-09-01
- Volume
- 179
- Issue
- 4
- Pages
- 233-243
- ISSN
- 0341-2040 (ISSN-L)
- OpenAlex
- W2041451562
- Cited by
- 74
- References
- 0
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 8 · 2013: 6 · 2012: 7
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Lung (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-60917)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Health Sciences › Medicine › Genetics › Vascular Anomalies and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- nitric oxide, pulmonary hypertension, epoprostenol, prostacyclin therapy, exhaled nitric oxide, idiopathic pulmonary arterial hypertension, secondary pulmonary hypertension, pulmonary artery pressure, right ventricular systolic pressure, disease severity markers, treatment response biomarkers
- MeSH terms
- Adolescent, Adult, Antihypertensive Agents, Breath Tests, Female, Humans, Hypertension, Pulmonary, Male, Middle Aged, Nitric Oxide, Epoprostenol, Vasodilator Agents, Biomarkers, Respiratory Mechanics
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