TY - JOUR T1 - Endothelins and pulmonary hypertension, what directions for the near future? JF - European Respiratory Journal JO - Eur Respir J SP - 1 LP - 4 DO - 10.1183/09031936.01.00002401 VL - 18 IS - 1 AU - S. Eddahibi AU - S. Adnot Y1 - 2001/07/01 UR - http://erj.ersjournals.com/content/18/1/1.abstract N2 - Among the various vasoactive molecules or growth factors that have been tentatively implicated in pulmonary hypertension (PH), endothelin (ET) is particularly important because the potential therapeutic efficacy of ET-receptor antagonists is being investigated in patients with PH 1. ET was discovered in 1988 and found to be the most potent vasoconstrictor ever known 2. The discovery that ET was abundantly expressed in the lung directed attention toward its potential role in the initiation or progression of PH. Beneficial effects of chronic treatment with specific ET-receptor antagonists in experimental PH were first reported in 1994–1995 3, 4. ET-receptor antagonists now hold considerable promise for the treatment of human PH 1, illustrating how fast basic research has moved to clinical use in this specific area.Experimental studies of the expression and effects of lung ET have contributed substantially to the current fund of knowledge about the pathophysiological role of ET in PH and are in good agreement with those obtained in human PH. The current understanding of the ET system in the pathogenesis of PH can be summarized as follows: 1) the ET system seems activated in all forms of human PH 5 and in all animal models of PH 6, 7; 2) ET may contribute to the development of PH through its potent vasoconstricting properties, or its promitogenic properties 8–10; 3) ET-receptor blockade protects against PH and, more convincingly, reverses established sustained experimental PH 3, 4, 11–14. Each of these effects has been documented by a large number of studies. However, several questions of crucial importance when considering ET as a therapeutic target remain unanswered. 1) Why is the lung ET system activated during PH? 2) Why is lung ET well tolerated in the normal lung … ER -