Regulation of Endothelin-1 at Rest and During a Short Steady-State Exercise in 21 COPD Patients

Faller, M; Kessler, Romain; Sapin, R; Chaouat, Ari; Ehrhart, M; Ducoloné, A; Weitzenblum, E

doi:10.1006/pupt.1998.0130

Cited by 19 publications

(13 citation statements)

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“…In addition, in the animal model of CB, the observed vasoconstriction could be explained also by a predominant action of endothelium-derived constricting factors. Decreased NO activity and increased plasma levels of ET-1 in response to hypoxemia have been described and also could explain the pulmonary arterial vasoconstriction and pulmonary hypertension observed in COPD (56,69). Thus, vasoconstriction of pulmonary vessels associated with CAPs exposures may be the result of an effect at the level of the pulmonary vascular endothelial cells with an abnormal balance between releasing of endothelium-derived constricting factors and endothelium-derived relaxing factors.…”

Section: Discussionmentioning

confidence: 99%

“…In animal studies, significant mortality associated with ambient or surrogate particle inhalation or intratracheal instillation has been observed only in models where there was a preexisting endothelial injury. Human epidemiologic studies show that the increased risk of death is greater in people with COPD (3), a disease process that includes some pulmonary endothelial dysfunction (69). Further studies of CAPs on the pulmonary arterial vasculature are needed to establish the full extent and the chronicity of these demonstrated effects.…”

Section: Discussionmentioning

confidence: 99%

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Concentrated Ambient Air Particles Induce Vasoconstriction of Small Pulmonary Arteries in Rats

Batalha¹

2002

Environ. Health Perspect.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Concentrated Ambient Air Particles Induce Vasoconstriction of Small Pulmonary Arteries in Rats

Batalha¹

2002

Environ. Health Perspect.

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“…Hypoxemia is a potent inducer of ET-1 in humans and experimental animals, 14,[32][33][34][35] and arterial pO 2 Ͻ65 mm Hg is associated with significant increases in plasma ET-1 in humans. 33 Furthermore, the degree of hypoxemia correlates with induction of pulmonary prepro-ET-1 mRNA expression in the AHR KO mice, although the levels remain significantly less than WT mice. Thus, the hypoxemia exhibited by AHR KO mice at modest altitude could be responsible for the increase observed in plasma ET-1 above the already elevated basal levels.…”

Section: Discussionmentioning

confidence: 99%

Loss of the Aryl Hydrocarbon Receptor Induces Hypoxemia, Endothelin-1, and Systemic Hypertension at Modest Altitude

et al. 2008

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Abstract-The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix Per-Arnt-Sim transcription factor that mediates induction of metabolic enzymes and toxicity of certain environmental pollutants. Although AHR knockout (KO) mice develop cardiac hypertrophy, conflicting reports associate this pathology with hypotension or endothelin (ET)-1-dependent hypertension. Because hypertension occurred at modest altitude, we tested the hypothesis that loss of AHR increases the sensitivity to hypoxia-induced ET-1, contributing to systemic hypertension. We found that AHR KO mice were hypertensive at modest altitude (1632 m) but hypotensive at low altitude (225 m). When AHR KO mice residing at 1632 m were exposed to the partial pressure of inspired oxygen (PIO 2 ) at sea level for 11 days, blood pressure declined to levels measured at 225 m. Although plasma ET-1 in AHR KO mice was significantly elevated at 1632 m and decreased at 225 m and sea level PIO 2 , pulmonary prepro-ET-1 mRNA was significantly reduced at 1632 m and decreased further at 225 m and sea level PIO 2 . Blood gas analysis revealed that AHR KO mice were hypoxemic, hypercapnic, and acidotic at 1632 m, values that were attenuated and normalized after 24 hours and 11 days under sea level PIO 2 , respectively. Lastly, AHR inactivation in endothelial cells by small interfering RNA significantly reduced basal prepro-ET-1 mRNA but did not alter hypoxia-induced expression. Our studies establish the AHR KO mouse as a model in which modest decreases in PIO 2 lead to hypoxemia, increased plasma ET-1, and systemic hypertension without increased pulmonary prepro-ET-1 mRNA expression. Key Words: blood pressure Ⅲ hypertension Ⅲ endothelin Ⅲ oxygen Ⅲ gene regulation T he aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor belonging to the basic helix-loophelix Per-Arnt-Sim family of DNA binding proteins, which also includes hypoxia-inducible factors. 1 Although the AHR is known to mediate induction of drug-metabolizing enzymes and toxicity after exposure to 2,3,7,8-tetrachlorodibenzo-pdioxin, recent evidence has revealed a physiological role for AHR in cardiovascular homeostasis. AHR knockout (KO) mice develop cardiac hypertrophy, 2,3 which is mediated, in part, by elevated plasma angiotensin II and endothelin-1 (ET-1). 4,5 There are conflicting reports, however, of whether the cardiac hypertrophy is associated with systemic hypertension. Lund et al 4,5 reported that cardiac hypertrophy in AHR KO mice is preceded by hypertension, whereas Vasquez et al 6 and Ichihara et al 7 reported that AHR KO mice are hypotensive and normotensive, respectively. The explanation for the disparate blood pressure values among these studies is unclear.AHR and hypoxia-inducible factor-1␣ share a common dimerization partner, AHR nuclear translocator (hypoxiainducible factor-1␤), as well as other transactivators, and studies have shown that these 2 signal transduction pathways can exhibit reciprocal inhibitory cross-talk. 8,9 The mechanism by which this functional inter...

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“…Plasma ET-1 concentrations are also elevated in COPD patients, particularly in patients who develop nocturnal hypoxemia during the night (Trakada et al, 2001;Spiropoulos et al, 2003) and in patients with hypoxemia (Faller et al, 1998), but it is not correlated with secondary pulmonary hypertension (Bacakoglu et al, 2003). This may reflect the release of ET-1 by hypoxemia, suggesting that the release of ET-1 may contribute to pulmonary vasoconstriction and pulmonary hypertension in COPD patients.…”

Section: Formationmentioning

confidence: 99%

Mediators of Chronic Obstructive Pulmonary Disease

2004

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Regulation of Endothelin-1 at Rest and During a Short Steady-State Exercise in 21 COPD Patients

Cited by 19 publications

References 5 publications

Concentrated Ambient Air Particles Induce Vasoconstriction of Small Pulmonary Arteries in Rats

Concentrated Ambient Air Particles Induce Vasoconstriction of Small Pulmonary Arteries in Rats

Loss of the Aryl Hydrocarbon Receptor Induces Hypoxemia, Endothelin-1, and Systemic Hypertension at Modest Altitude

Mediators of Chronic Obstructive Pulmonary Disease

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