Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease?
OBJECTIVE
To explore the role of endothelin-1, a potent endothelial-derived vasoconstrictor peptide, in pulmonary hypertension, by measuring its concentration in arterial and venous plasma.


METHODS
A survey, case series study.


METHODS
University-affiliated hospitals and outpatient clinics.


METHODS
Twenty-seven patients with pulmonary hypertension: 7 with primary, and 20 with secondary pulmonary hypertension of various causes. The control groups (n = 16) comprised 8 healthy volunteers and 8 patients with coronary artery disease but without evidence of pulmonary hypertension.


RESULTS
Pulmonary artery pressure was markedly increased (94/43 +/- 23/13 mm Hg) in the patients with pulmonary hypertension. Venous plasma immunoreactive endothelin-1, measured by a specific radioimmunoassay, was significantly higher in patients with pulmonary hypertension (3.5 +/- 2.5 pg/mL, P less than 0.001) than in normal subjects (1.45 +/- 0.45 pg/mL), or patients with coronary disease (0.75 +/- 0.64 pg/mL). The arterial-to-venous ratio of immunoreactive endothelin-1 was significantly greater than unity in primary pulmonary hypertension (2.21 +/- 0.72, P = 0.01), whereas the patients with secondary pulmonary hypertension had a mean ratio not different from 1 (0.97 +/- 0.42). In contrast, the mean arterial-to-venous ratios were significantly less than unity in both control groups (0.59 +/- 0.35, and 0.54 +/- 0.64; P less than 0.02, for normal subjects and coronary disease patients, respectively), indicating a possible clearance of endothelin-1 across the healthy lung.


CONCLUSIONS
Patient with pulmonary hypertension have substantial alterations in plasma immunoreactive endothelin-1, which may reflect changes in net release or clearance of endothelin-1 by the lung. In patients with primary pulmonary hypertension, the high levels in arterial compared with venous plasma suggest pulmonary production of endothelin-1, which may contribute to elevated pulmonary vascular resistance.
Stewart
D J
DJ
Division of Cardiology, Royal Victoria Hospital, Montreal, Quebec.
Levy
R D
RD
Cernacek
P
P
Langleben
D
D
D000328:Adult; D001158:Arteries; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood; D016232:Endothelins / Q000097:blood*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000209:etiology; D008875:Middle Aged; D011863:Radioimmunoassay; D012016:Reference Values; D014680:Veins
D015415:Biomarkers; D016232:Endothelins