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

Background. Pulmonary hypertension is characterized by an increase in vascular tone or an abnormal proliferation of muscle cells in the wall s of small pulmonary arteries. Endothelin-1 is a potent endothelium-de rived vasoconstrictor peptide with important mitogenic properties. It has therefore been suggested that endothelin-1 may contribute to incre ases in pulmonary arterial tone or smooth-muscle proliferation in pati ents with pulmonary hypertension. We studied the sites and magnitude o f endothelin-1 production in the lungs of patients with various causes of pulmonary hypertension. Methods. We studied the distribution of en dothelin-1-like immunoreactivity (by immunocytochemical analysis) and endothelin-1 messenger RNA (by in situ hybridization) in lung specimen s from 15 control subjects, 11 patients with plexogenic pulmonary arte riopathy (grades 4 through 6), and 17 patients with secondary pulmonar y hypertension and pulmonary arteriopathy of grades 1 through 3. Resul ts. In the controls, endothelin-1-like immunoreactivity was rarely see n in vascular endothelial cells. In the patients with pulmonary hypert ension, 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 primaril y at sites of endothelin-1-like immunoreactivity. There was a strong c orrelation between the intensity of endothelin-1-like immunoreactivity and pulmonary vascular resistance in the patients with plexogenic pul monary arteriopathy, but not in those with secondary pulmonary hyperte nsion. Conclusions. Pulmonary hypertension is associated with the incr eased expression of endothelin-1 in vascular endothelial cells, sugges ting that the local production of endothelin-1 may contribute to the v ascular abnormalities associated with this disorder.