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Previous Volume 328:1732-1739 June 17, 1993 Number 24 Next

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ABSTRACT

Background Pulmonary hypertension is characterized by an increase in vascular tone or an abnormal proliferation of muscle cells in the walls of small pulmonary arteries. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide with important mitogenic properties. It has therefore been suggested that endothelin-1 may contribute to increases in pulmonary arterial tone or smooth-muscle proliferation in patients with pulmonary hypertension. We studied the sites and magnitude of endothelin-1 production in the lungs of patients with various causes of pulmonary hypertension.

Methods We studied the distribution of endothelin-1-like immunoreactivity (by immunocytochemical analysis) and endothelin-1 messenger RNA (by in situ hybridization) in lung specimens from 15 control subjects, 11 patients with plexogenic pulmonary arteriopathy (grades 4 through 6), and 17 patients with secondary pulmonary hypertension and pulmonary arteriopathy of grades 1 through 3.

Results In the controls, endothelin-1-like immunoreactivity was rarely seen in vascular endothelial cells. In the patients with pulmonary hypertension, endothelin-1-like immunoreactivity was abundant, predominantly in endothelial cells of pulmonary arteries with medial thickening and intimal fibrosis. Likewise, endothelin-1 messenger RNA was increased in the patients with pulmonary hypertension and was expressed primarily at sites of endothelin-1-like immunoreactivity. There was a strong correlation between the intensity of endothelin-1-like immunoreactivity and pulmonary vascular resistance in the patients with plexogenic pulmonary arteriopathy, but not in those with secondary pulmonary hypertension.

Conclusions Pulmonary hypertension is associated with the increased expression of endothelin-1 in vascular endothelial cells, suggesting that the local production of endothelin-1 may contribute to the vascular abnormalities associated with this disorder.

Source Information

From the Departments of Pathology (A.G., R.P.M., W.P.D.), Medicine (D.L., R.L., D.J.S.), and Surgery (H.S.), McGill University, Montreal; the Howard Hughes Medical Institute and Department of Molecular Genetics, University of Texas Southwest Medical Center, Dallas (M.Y.); Kyoto University, Kyoto, Japan (T.M.); and the Faculty of Medicine, Chiba University, Chiba, Japan (S.K.).

Address reprint requests to Dr. Giaid at the Dept. of Pathology, Montreal General Hospital, 1650 Cedar Ave., Montreal, QC H3G 14A, Canada.

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Endothelin-1 in Pulmonary Hypertension
Cacoub P., Dorent R., Nataf P., Carayon A., Giaid A.
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N Engl J Med 1993; 329:1967-1968, Dec 23, 1993. Correspondence

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