Arterial endothelin-1 level in pulmonary emphysema and interstitial lung disease. Relation with pulmonary hypertension during exercise

Abstract

Arterial endothelin-1 level in pulmonary emphysema and interstitial lung disease. Relation with pulmonary hypertension during exercise. T. Yamakami, O. Taguchi, E.C. Gabazza, M. Yoshida, T. Kobayashi, H. Kobayashi, H. Yasui, H. Ibata, Y Adachi. ERS Journals Ltd 1997. ABSTRACT: This study was undertaken to assess the arterial plasma levels of endothelin-1 (ET-1) and their relationship with pulmonary haemodynamic and gas exchange variables during exercise in patients with emphysema and interstitial lung disease (ILD).Incremental cycle ergometry was performed in all patients up to maximal capacity. At rest, arterial ET-1 levels were higher in emphysema (1.86±0.35 pg·mL -1 ; p<0.02) and ILD (1.75±0.25 pg·mL -1 ; p<0.03) patients than in controls (1.35±0.18 pg·mL -1 ). Emphysema (2.08±0.26 versus 1.70±0.40 pg·mL -1 ) and ILD (1.98±0.21 versus 1.67±0.02 pg·mL -1 ) patients with pulmonary hypertension (PH) presented significantly (p<0.05) higher arterial ET-1 levels than those without. At rest, arterial ET-1 levels were significantly correlated with mean pulmonary arterial pressure (Ppa) in both ILD (r=0.8, p=0.01) and emphysema (r=0.5, p=0.03) patients. During exercise, the arterial ET-1 levels were significantly correlated with arterial oxygen (Pa,O 2 ) (r=-0.6, p=0.04), alveolar-arterial oxygen difference (r=0.8, p=0.01), and Ppa (r=0.6, p=0.04) in ILD patients, but not in those with emphysema.In brief, the results of this study suggest that arterial endothelin-1 is markedly increased in interstitial lung disease and emphysema patients, and that, it is related to the exercise-induced exacerbation of pulmonary hypertension in patients with interstitial lung disease, but not in those with emphysema. Eur Respir J 1997; 10: 2055-2060. Pulmonary artery hypertension is the major cardiovascular complication of emphysema and advanced interstitial lung disease (ILD) [1]. Pulmonary hypertension (PH) is important, not only because it is associated with right ventricular hypertrophy (or cor pulmonale) but also because it adversely affects prognosis in these patients [2]. The mechanisms responsible for PH include thrombotic obstruction of pulmonary blood vessels, reduced distensibility of the pulmonary vascular bed, pulmonary vascular obstruction produced by medial hypertrophy or intimal proliferation, and pulmonary vasoconstriction elicited by acute or chronic alveolar hypoxia [3,4]. Of these, hypoxic vasoconstriction has been considered one of the major factors involved in the pathogenesis of sustained PH or in the development of acute exacerbation of PH in patients with emphysema or advanced ILD [5]. However, the precise mechanism by which hypoxia induces pulmonary vasoconstriction and the structural changes that ensue from chronic hypoxia have not been fully elucidated. Endothelin-1 (ET-1), a vasoconstricting peptide originally isolated from cultured human endothelial cells, may play a relevant role in the pathogenesis of PH during hypoxia [6][7][8]. This assumption is supported by previous findings that showed that the e...

Mechanisms of Endothelin-1 Elevation in Chronic Obstructive Pulmonary Disease Patients with Nocturnal Oxyhemoglobin Desaturation

“…In agreement with previous studies, we found that the nondesaturator COPD patients had higher levels of PaO 2 and lower levels of ET-1 than the desaturators when awake [55, 57, 58]. Tatsuo et al [59]found that plasma ET-1 levels were not affected by acute progression of hypoxia and pulmonary hypertension in COPD patients during exercise.…”

“…This vasoconstricting peptide may play a relevant role in the pathogenesis of pulmonary hypertension [47, 48, 49]. Increased pulmonary and peripheral blood levels of ET-1 have been described in primary pulmonary hypertension, bronchial asthma, acute lung injury, fibrosing alveolitis, interstitial lung disease and emphysema [50, 51, 52, 53, 54, 55, 56]. Yamakami et al [55]performed cycle ergometry and found that ET-1 levels were statistically significantly correlated with arterial oxygen fall in interstitial lung disease patients.…”

Effect of bosentan on the production of proinflammatory cytokines in a rat model of emphysema

“…It is known that the circulating levels of ET-1 increased in patients with emphysema, and endothelins act as proinflammatory agents (Yamakami et al, 1997). In vitro, ET-1 has been shown to stimulate the release of the cytokines TNF-α, IL-1β, IL-6, and IL-8 (Helset et al, 1993;Huribal et al, 1994), and a study showed that ET-1 antagonism strongly inhibited the production of these cytokines within the airways (Finsnes et al, 2001).…”

Pulmonary hypertension in interstitial lung disease

“…2) Formation of alveolar fibrin clots due to impaired intra-alveolar fibrinolysis providing a lead structure for fibroblast chemotactic migration and proliferation as well as for neovascularisation [29,30,43]. 3) Growth factors such as TGF-b, insulin-like growth factor-1, platelet-derived growth factor (PDGF) and CTGF play a crucial role in the expansion of connective tissue and vascular remodelling in the lungs [44][45][46][47][48][49][50][51]. 4) Epithelial cell apoptosis and impaired epithelial regeneration and epithelial-to-mesenchymal transdifferentiation linked to integrin signalling promotes fibrotic tissue remodelling [52,53].…”