Increased Plasma Endothelin-1 in Pulmonary Hypertension: Marker or Mediator of Disease?

TLDR

The study investigates endothelin‑1 levels in arterial and venous plasma to determine its role in pulmonary hypertension. The authors conducted a case‑series survey of 27 pulmonary hypertension patients and 16 controls, measuring arterial and venous endothelin‑1 concentrations and pulmonary artery pressures. Patients with pulmonary hypertension exhibit markedly elevated venous endothelin‑1 and, in primary disease, an arterial‑to‑venous ratio >1, indicating pulmonary production and impaired clearance that may raise vascular resistance.

Abstract

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.A survey, case series study.University-affiliated hospitals and outpatient clinics.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.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.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.