Circulating endothelin-1 concentrations in patients with chronic hypoxia.

Ferri, Claudio; Bellini, Cesare; Angelis, Claudio De; Siati, Luca De; Perrone, Anna; Properzi, Giuliana; Santucci, A.

doi:10.1136/jcp.48.6.519

Cited by 68 publications

(43 citation statements)

References 26 publications

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“…However, all relevant studies are consistent in showing that the ET-1 levels are significantly increased in cases of pulmonary hypertension. The most dramatic increases in circulating ET-1 levels and ET-1 expression, appear to be associated with primary pulmonary hypertension (Stewart et al, 1991;Cacoub et al, 1993;Giaid et al, 1993;Nootens et al, 1995); although ET-1 levels are also significantly increased in pulmonary hypertension secondary to hypoxia (Stewart et al, 1991;Ferri et al, 1995), congenital heart defects (Yoshibayashi et al, 1991;Cacoub et al, 1993;Vincent et al, 1993), valvular heart disease (Stewart et al, 1991;Chang et al, 1993;Yamamoto et al, 1994;Zhu et al, 1994), chronic heart failure (Cody et al, 1992;Kiowski et al, 1995) and the adult respiratory distress syndrome (Langleben et al, 1993). Plasma ET-1 levels can be increased four fold in some of these studies.…”

Section: Resultsmentioning

confidence: 99%

Endothelin_B receptor‐mediated contraction in human pulmonary resistance arteries

McCulloch

Docherty

Morecroft

et al. 1996

British J Pharmacology

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Using wire myography, we have examined the endothelin (ET) receptor subtypes mediating vasoconstriction to ET peptides in human pulmonary resistance arteries (150–200 μm, i.d.). Cumulative concentration‐response curves to ET‐1, sarafotoxin 6c (SX6c) and ET‐3 were constructed in the presence and absence of the selective antagonists FR 139317 (ETA‐selective), BMS 182874 (ETA‐selective) and BQ‐788 (ETB‐selective). All agonists induced concentration‐dependent contractions. However, the response curves to ET‐1 were biphasic in nature. The first component demonstrated a shallow slope up to 1 nM ET‐1. Above 1 nM ET‐1 the response curve was markedly steeper. Maximum responses to ET‐3 and SX6c were the same as those to 1 nM ET‐1 and 30% of those to 0.1 μm ET‐1. The order of potency, taking 0.3 μm as a maximum concentration was SX6c > > ET‐3 > ET‐1 (pEC50 values of: 10.75 ± 0.27, 9.05 ± 0.19, 8.32 ± 0.08 respectively). Taking 1 nM ET‐1 as a maximum, the EC50 for ET‐1 was 10.08 ± 0.13 and therefore ET‐1 was equipotent to ET‐3 and SX6c over the first component of the response curve. Responses to ET‐1 up to 1 nM were resistant to the effects of the ETA receptor antagonists, FR 139317 and BMS 182874 but were inhibited by the ETB receptor antagonist, BQ‐788. Conversely, responses to ET‐1 over 1 nM were inhibited by the ETA receptor antagonists, FR 139317 and BMS 182874 but unaffected by the ETB receptor antagonist, BQ‐788. The results suggest that at concentrations up to 1 nM, responses to ET‐1 are mediated via the ETB receptor, whilst the responses to higher concentrations are mediated by ETA receptors.

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Section: Resultsmentioning

confidence: 99%

Endothelin_B receptor‐mediated contraction in human pulmonary resistance arteries

McCulloch

Docherty

Morecroft

et al. 1996

British J Pharmacology

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“…ET-1 was identified in 1989 in human plasma by radioimmunoassay [5], and its level was found to be increased in several diseases, such as atherosclerosis [4], myocardial infarction [6], renal disease [7], and systemic [8]and pulmonary hypertension [9]. Recent studies have shown that the plasma ET-1 level is increased in patients with COPD compared with normal subjects [10, 11]. However, the pathophysiological roles of the increase in plasma ET-1 level in patients with COPD remain incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

Plasma Endothelin-1 Level in Chronic Obstructive Pulmonary Disease: Relationship with Natriuretic Peptide

Fujii

Otsuka²,

Tanaka³

et al. 1999

Respiration

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Background and Objective: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by the vascular endothelium. The purpose of this study was to elucidate the pathophysiological role of ET-1 in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD). Method: We measured plasma ET-1 levels during right heart catheterization both at rest and during exercise on room air and while breathing oxygen in patients with COPD. In addition, we simultaneously measured plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Results: Plasma ET-1 levels at rest were significantly higher in 21 patients with COPD than in 16 control subjects (p < 0.001). For COPD patients, there was no correlation between the plasma ET-1 level and pulmonary arterial pressure or pulmonary vascular resistance at rest. On the other hand, there was a significant negative correlation between plasma ET-1 level and mixed venous oxygen tension (r = –0.503, p < 0.05). Also, the plasma ET-1 level was positively correlated with those of ANP (r = 0.540, p < 0.05) and BNP (r = 0.533, p < 0.05) at baseline. Oxygen administration significantly decreased plasma ET-1 levels at rest (p < 0.05). Plasma ET-1 levels did not change significantly with exercise despite the progression of pulmonary hypertension and hypoxemia. In contrast, plasma ANP and BNP levels both increased markedly with exercise (p < 0.01). Conclusion: We conclude that in patients with COPD, the plasma ET-1 level is not affected by acute progression of pulmonary hypertension and hypoxemia during exercise, and persistent hypoxemia may be associated with an increase in the plasma ET-1 level. In addition, our findings suggest that ANP and BNP may modulate the pulmonary vascular tone by interacting with ET-1 in these patients.

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“…Furthermore, chronic hypoxia is a condition with elevated ET-1 plasma levels 6 and in a rat model of chronic hypoxia enhanced ET-1 and endothelin receptor expression was found. 7 Conflicting data, however, exist on the effect of acute hypoxia on the release of ET-1.…”

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confidence: 99%

Exhaustive exercise-induced tissue hypoxia does not change endothelin and big endothelin plasma levels in normal volunteers

Lenz

Nadansky²,

Goßmann³

et al. 1998

American Journal of Hypertension

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Chronic hypoxia has been shown to increase plasma endothelin levels. The current study was undertaken to examine the effect of exerciseinduced tissue hypoxia on plasma levels of endothelin-1 (ET-1) and its precursor big endothelin-1 (Big-ET-1). After approval by the local ethical committee an incremental dynamic exercise test was performed in 12 physically trained volunteers (aged 20 to 40 years), using an electrically braked bicycle ergometer. The protocol included a step-wise increase of the workload until a heart rate of 130/min was reached, followed by a maintenance period of 25 min, and a further stepwise increase until exhaustion. Blood was drawn before, at several time points during, and 5 min after termination of the study for determination of ET-1, Big-ET-1, plasma renin activity (PRA), angiotensin converting enzyme (ACE), norepinephrine, epinephrine, and lactate. Lactate levels at baseline were 14.5 ؎ ؎ 1.6 mg/dL (mean ؎ ؎ SEM), which increased to 76.5 ؎ 4.8 mg/dL at the time of exhaustion (P < < .01). Baseline values for ET-1 and Big-ET-1 were 0.264 ؎ ؎ 0.061 and 0.637 ؎ ؎ 0.130 fmol/ml, respectively, which remained essentially unaltered throughout the exercise test. PRA was 1.46 ؎ ؎ 0.45 ng/mL/h before exercise and increased to 3.55 ؎ ؎ 0.96 ng/mL/h at exhaustion (P < < .001). Norepinephrine and epinephrine were also increased at exhaustion. The study demonstrates that exhaustive physical exercise with acute development of pronounced tissue hypoxiain contrast to chronic hypoxia-does not influence the release of ET-1 or Big-ET-1 or the conversion of the precursor to the active compound. Unlike endothelin, circulating renin and the catecholamines were markedly stimulated by this maneuver. Am

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Circulating endothelin-1 concentrations in patients with chronic hypoxia.

Cited by 68 publications

References 26 publications

Endothelin_B receptor‐mediated contraction in human pulmonary resistance arteries

Endothelin_B receptor‐mediated contraction in human pulmonary resistance arteries

Plasma Endothelin-1 Level in Chronic Obstructive Pulmonary Disease: Relationship with Natriuretic Peptide

Exhaustive exercise-induced tissue hypoxia does not change endothelin and big endothelin plasma levels in normal volunteers

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Circulating endothelin-1 concentrations in patients with chronic hypoxia.

Cited by 68 publications

References 26 publications

EndothelinB receptor‐mediated contraction in human pulmonary resistance arteries

EndothelinB receptor‐mediated contraction in human pulmonary resistance arteries

Plasma Endothelin-1 Level in Chronic Obstructive Pulmonary Disease: Relationship with Natriuretic Peptide

Exhaustive exercise-induced tissue hypoxia does not change endothelin and big endothelin plasma levels in normal volunteers

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Endothelin_B receptor‐mediated contraction in human pulmonary resistance arteries

Endothelin_B receptor‐mediated contraction in human pulmonary resistance arteries