Decreased Exhaled Nitric Oxide in Pulmonary Arterial Hypertension

Girgis, Reda E.; Champion, Hunter C.; Diette, Gregory B.; Johns, Roger A.; Permutt, Solbert; Sylvester, J. T.

doi:10.1164/rccm.200412-1684oc

Cited by 131 publications

(138 citation statements)

References 52 publications

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“…It comes primarily from airway epithelial cells with a component from the pulmonary vasculature [61]. Exhaled NO (eNO) has been shown to be lower in patients with IPAH [62][63][64], although there are conflicting studies that show either no difference in eNO compared with controls [65,66] or an increased level [67]. These divergent results could be explained by methodological differences.…”

Section: Nitric Oxidementioning

confidence: 99%

“…When measured in the bronchoalveolar lavage fluid of patients with IPAH, biochemical reaction products of NO (nitrate, nitrite and S-nitrosothiol proteins) are significantly lower than in control patients and correlate inversely with pulmonary artery pressures and duration of PAH [63]. eNO levels increase after initiation of intravenous [64] and inhaled [65] prostacyclin therapy, and also after established treatment with bosentan, a nonselective ET receptor antagonist [62]. In interpreting eNO results, the physician must take into account a number of potential confounding factors including age, sex, atopy, infection and some drugs, including some used in the treatment of PH, such as L-arginine [68].…”

Section: Nitric Oxidementioning

confidence: 99%

“…Serum uric acid levels decrease with successful treatment with prostacyclin of patients with IPAH [54]. Exhaled NO may be useful in the long-term monitoring of patients on prostacyclin [89] and bosentan [62].…”

Section: Response To Therapymentioning

confidence: 99%

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Biomarkers in pulmonary hypertension

Warwick

Thomas²,

Yates³

2008

Eur Respir J

140

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There have been significant recent advances in the understanding of the pathophysiology of pulmonary hypertension, and a growing number of therapeutic agents have become available to the treating physician. Traditional methods of diagnosing and monitoring this condition have comprised echocardiography and right heart catheterisation, in addition to functional measures, such as estimation of functional class and the 6-min walk test. An increasing number of biomarkers have been described that are elevated in pulmonary hypertension and which may assist the clinician in diagnosis and in the assessment of disease severity and response to treatment.The present article details the more important biomarkers, their potential applications and the evidence supporting their use.

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Section: Nitric Oxidementioning

confidence: 99%

Section: Nitric Oxidementioning

confidence: 99%

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Biomarkers in pulmonary hypertension

Warwick

Thomas²,

Yates³

2008

Eur Respir J

140

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show abstract

“…Most studies of NO in PAH patients have measured exhaled NO levels from the lungs in order to assess possible changes in NO synthesis in PAH [284][285][286][287][288][289][290]. NO is relatively stable in the gas phase, allowing for such measurements, whereas the instability of NO in biological �uids means that estimates of NO synthesis from blood measurements are usually done via nitrate/nitrite products derived from NO.…”

Section: No Elevation?mentioning

confidence: 99%

“…e majority of studies on exhaled NO in PAH patients report lowered levels when compared with controls [284][285][286][287]289], but two such studies report apparent elevated levels, with one reporting a nonsigni�cant trend [288] and the other signi�cant elevation [290]. Consequently, there appears to be substantial variation in these studies.…”

Section: No Elevation?mentioning

confidence: 99%

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

Pall

2013

ISRN Hypertension

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e NO/ONOO − cycle is a primarily local biochemical/physiological vicious cycle that appears to cause a series of chronic in�ammatory diseases. is paper focuses on whether the cycle causes pulmonary arterial hypertension (PAH) when located in the pulmonary arteries. e cycle involves 12 elements, including superoxide, peroxynitrite (ONOO − ), nitric oxide (NO), oxidative stress, NF-B, in�ammatory cytokines, iNOS, mitochondrial dysfunction, intracellular calcium, tetrahydrobiopterin depletion, NMDA activity, and TRP receptor activity. 10 of the 12 are elevated in PAH (NMDA?, NO?) and 11 have documented causal roles in PAH. Each stressor that initiates cases of PAH acts to raise cycle elements, and may, therefore, initiate the cycle in this way. PAH involves a primarily local mechanism as required by the cycle and the symptoms and signs of PAH are generated by elements of the cycle. Endothelin-1, which acts as a causal factor in PAH, acts as part of the cycle; its synthesis is stimulated by cycle elements, and it, in turn, increases each element of the cycle. is extraordinary �t to the principles of the NO/ONOO − cycle allows one to conclude that PAH is a NO/ONOO − cycle disease, and this �t supports the cycle as a ma�or paradigm of chronic in�ammatory disease.

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Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis

Sfikakis¹,

Papamichael

Stamatelopoulos

et al. 2007

Arthritis & Rheumatism

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Objective. Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients.Methods. A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel.Results. FMD%, the main end point, increased significantly from a mean ؎ SD of 3.1 ؎ 1.3% to 8.4 ؎ 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 ؎ 1.6% to 2.4 ؎ 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n ‫؍‬ 5) or increased to 250 mg/day (n ‫؍‬ 5), the 4-week results remained unchanged.Conclusion. Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted.

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Decreased Exhaled Nitric Oxide in Pulmonary Arterial Hypertension

Abstract: FE(NO) at low expiratory flows was decreased in PAH due to reduced C(W). Bosentan reversed these abnormalities, suggesting that suppression of NO in PAH may have been caused by endothelin.

Cited by 131 publications

References 52 publications

Biomarkers in pulmonary hypertension

Biomarkers in pulmonary hypertension

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review

Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis

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Decreased Exhaled Nitric Oxide in Pulmonary Arterial Hypertension

Abstract: FE(NO) at low expiratory flows was decreased in PAH due to reduced C(W). Bosentan reversed these abnormalities, suggesting that suppression of NO in PAH may have been caused by endothelin.

Cited by 131 publications

References 52 publications

Biomarkers in pulmonary hypertension

Biomarkers in pulmonary hypertension

Pulmonary Hypertension Is a Probable NO/ONOO−Cycle Disease: A Review

Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis

Contact Info

Product

Resources

About

Pulmonary Hypertension Is a Probable NO/ONOO⁻Cycle Disease: A Review