Regulation of endothelin-1 at rest and during a short steady-state exercise in 21 COPD patients

Endothelin-1 (ET-1) is a vasoconstrictive peptide which may play a relevant role in the pathogenesis of pulmonary hypertension (PH) in COPD patients. We assessed the correlations of plasmatic ET-1 levels with pulmonary function data, arterial blood gases and pulmonary haemodynamics in 21 COPD patients with moderate to severe airway obstruction (FEV1: 1.19 +/- 0.49 I, mean+/-SD). There were 11 hypoxemic patients (PaO2 <65 mmHg). Six patients had resting PH (mean pulmonary artery pressure greater than or equal to 20 mmHg). Eight patients had exercising PH (PAP greater than or equal to 30 mmHg) during a short (6 min) 30 W steady state exercise. At rest, arterial ET-1 levels were significantly higher in COPD patients with hypoxemia when compared to those without hypoxemia (16.6+/-2.7 vs. 12.5+/-3.9 pM/l, P=0.02) and in COPD patients with PH when compared to those without PH (16.5+/-3.4 vs. 13+/-3.9 pM/l, P=0.04). Resting arterial ET-1 levels were negatively correlated with PaO2 (r=-0.45, P=0.05). At rest, the differences between mixed venous and arterial ET-1 levels were positively correlated with FEV, (r=0.54, P=0.024). At exercise, the mean arterial ET-1 level was not significantly different from the mean resting ET-1 level (13.8+/-3.4 vs. 13.3+/-4 pM/l, NS). There were eight COPD patients who had decreasing arterial ET-1 levels between rest and the end of a 6 min exercise, and six COPD patients who had increasing arterial ET-1 levels. These variations of arterial systemic ET-1 levels from rest to exercise were negatively correlated with FEV1 (r = -0.66, P=0.01). We conclude that in COPD patients (1) at rest, arterial ET-1 levels are increased in hypoxemia or pulmonary hypertension and (2) at rest or during exercise, the turn-over of ET-1 may be dependent of the degree of the bronchial obstruction. (C) 1998 Academic Press.