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(Circulation. 2002;105:1034.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Selective Upregulation of Endothelin B Receptor Gene Expression in Severe Pulmonary Hypertension

Michael Bauer, MD; Heinrike Wilkens, MD; Frank Langer, MD; Sven O. Schneider, BS; Henning Lausberg, MD; Hans-Joachim Schäfers, MD

From the Departments of Anesthesiology and Critical Care Medicine (M.B., S.V.O.), Internal Medicine V (H.W.), and Thoracic and Cardiovascular Surgery (F.L., H.L., H.-J.S.), University of the Saarland, Homburg, Germany.

Correspondence to Michael Bauer, MD, Department of Anesthesiology and Critical Care Medicine, University of the Saarland, D-66421 Homburg, Germany. E-mail aimbau{at}uniklinik-saarland.de

Background— The pulmonary circulation is an important site for the production and clearance of endothelin (ET)-1, a potent vasoactive and mitogenic peptide. Increased plasma ET-1 levels are observed in pulmonary arterial hypertension (PHT) and may contribute to the regulation of pulmonary vascular resistance, as well as to proliferative changes in the pulmonary vascular bed.

Methods and Results— We prospectively assessed changes in plasma big ET-1 levels and changes in ET_A and ET_B receptor gene expression in 14 consecutive patients undergoing pulmonary thromboendarterectomy for thromboembolic PHT. Plasma big ET-1 levels were higher in patients with PHT (median, 2.2 pg/mL; 25th to 75th percentile, 1.5 to 3.0 pg/mL) compared with age-matched controls (median, 1.2 pg/mL; 25th to 75th percentile, 1.0 to 1.4 pg/mL; P=0.002). In addition to increased plasma big ET-1 levels, selective upregulation of ET_B receptor mRNA transcripts and immunoreactive protein in the pulmonary artery was observed in the patients; however, ET_A receptor gene expression was unaffected.

Conclusions— These data suggest that changes in the ET signaling system in PHT caused by thromboembolic disease are not limited to an increased production of ET-1: they also affect ET receptor gene expression.

Key Words: pulmonary heart disease • hypertension, pulmonary • receptors

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