ENDOTHELIN-1 IN THE LUNGS OF PATIENTS WITH PULMONARY-HYPERTENSION

Background: Pulmonary hypertension (PH) is characterized by an increas e in vascular tone and an abnormal proliferation of muscle cells in th e waifs of pulmonary arteries. Recent studies have found high plasma e ndothelin-1 (ET-1) concentrations in patients with PH, This study was conducted to assess whether elevated circulating ET-1 levels in PH rea lly reflect excessive local pulmonary production. Methods: We prospect ively studied ET-1 concentration in lung specimens from 6 control subj ects and 13 patients with severe PH referred for lung or heart-lung tr ansplantation (6 patients had primary PH and 7 PH secondary to congeni tal heart defect). Endothelin-like immunoreactivity (ET-LI) was measur ed in plasma and lung tissue, using a radioimmunoassay, after ET-1 ext raction. Reverse-phase high-performance liquid chromatography was also performed. Results: Peripheral venous plasma ET-LI concentrations in patients with PH, whatever the cause, were greater than those in contr ols (10.7 +/- 0.8 vs 5.3 +/- 0.7 pg/ml; P < 0.0005). Pulmonary ET-LI w as significantly higher in patients with PH, irrespective of its cause , than in controls (25.2 +/- 5.1 vs 8.1 +/- 1.1 pg/mg, P < 0.03). ET-L I pulmonary concentrations were slightly higher in Eisenmenger than in primary PH, but this was not significant (27.1 +/- 8.6 vs 22.8 +/- 5. 4 pg/mg). Linear regression analysis indicated a small but significant correlation between ET-bl pulmonary concentrations and pulmonary vasc ular resistance in the patients with PH (r = 0.38; P = 0.047). In each case, HPLC separation of ET indicated that most of the immunoreactivi ty was detected in the same fraction as ET-1. Conclusions: The strikin g increase in ET-1 pulmonary concentration provides new evidence that excessive local pulmonary ET-1 production may contribute to the vascul ar abnormalities of pulmonary hypertension.