Abstract
The endothelin system has been extensively studied over the last several years. It is clear that endothelin-1 (ET-1) is a key mediator in pulmonary vascular biology and physiology. Abnormal increases in ET-1 production and decreased pulmonary clearance appear to play a major pathogenetic and perpetuating role in the pulmonary hypertensive process, through their vasconstrictive, smooth muscle cell proliferative and profibrotic effects. The degree of overexpression of ET-1 may correlate with the severity of pulmonary hypertension (PH). Advances in understanding the role of ET-1 in pulmonary hypertension have driven the development of endothelin receptor antagonists. One such agent, bosentan (Tracleer), is FDA approved for pulmonary arterial hypertension. Bosentan was approved following two randomized, placebo-controlled, double-blind studies that both showed marked improvement in exercise capacity after treatment with bosentan. The beneficial effects of bosentan appear to be sustained in most patients followed for as long as 22 months. Other uses for endothelin receptor antagonists are being examined, such as in combination with epoprostenol (Flolan) or in pediatric PH patients.
Idiopathic pre-capillary pulmonary hypertension in patients with end-stage kidney disease: effect of endothelin receptor antagonists
