Endothelin1 in Chronic Obstructive Pulmonary Disease: Relationship with Pulmonary Hypertension

Pulmonary Hypertension (PH) occurs often in patients affected by advanced COPD leading to respiratory failure and death. Endothelin1 (ET1) seems to be involved in the pathogenesis of vasospatic response to hypoxaemia and remodeling. COPD was divided into GOLD stages according to a progressive worsening of airways obstruction. Our aim was to measure ET1 in the different GOLD stages and to look for any relationship between ET1 and pulmonary vessels involvement assessed by Pulmonary Artery Pressure(PAP) and by vessel loss . Patients affected by COPD with (n=39) and without (n=39) PH were studied in a stable state and divided into three groups belonging to stage I-II, III and IV GOLD stages, respectively. Each subset was compared to healthy people (n=13). Airways obstruction was measured by pletismography, haemodynamics by catheterization of pulmonary artery, vessel pruning by perfusion scintigraphy, and ET1 levels by double-sandwich immunoassay over peripheral, arterial and mixed venous samples .ET1 increases in COPD IV stage with PH (1.3+.8 pg/l vs .28+.2 in healthy people). ET1 is significantly related to PAP in COPD with PH and increased in night-time desaturators and in hypercapnic patients. Unperfused scintigraphic areas are proportional to GOLD stages, but do not allow the separation between normotensive and hypertensive patients. PAP increased in the progressive stages of patients with PH. A transpulmonary gradient of ET1 can be appreciated in patients with PH. Both ET1 and PAP increase in advanced stages of COPD, during night-time hypoxemia, under effort and acute relapses. ET1 appears to be related to the development of PH in the advanced stages of the disease and its action is not mediated by the loss of pulmonary vessels, but is likely due to intrinsic changes of arterioles in susceptible patients.