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Semin Respir Crit Care Med 2005; 26(4): 402-408
DOI: 10.1055/s-2005-916155
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Endothelin Antagonism in Pulmonary Arterial Hypertension

Stephen H. Lee1 , Richard N. Channick1
  • 1Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California, San Diego, La Jolla, California
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Publication History

Publication Date:
25 August 2005 (online)

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ABSTRACT

The pathobiology of pulmonary arterial hypertension (PAH) reflects a multifactorial process and complex evolution that involves dysfunction of underlying cellular pathways and mediators. Among these, the endothelin system has been shown to be important in the pathogenesis of PAH. Endothelin-1 (ET-1), which is found in high levels in PAH, is a known potent vasoconstrictor with proliferative vascular remodeling properties. Left unchecked, endothelin excess, along with other derangements, may contribute to the development and perpetuation of PAH. There is now substantial evidence from clinical trials and long-term data that monotherapy with an endothelin receptor antagonist (ERA) is a beneficial, therapeutic approach in PAH. Combination therapy of an ERA with a prostanoid or phosphodiesterase-5 inhibitor, two drug classes that have different mechanisms of action, is conceptually appealing, but the evidence for its efficacy and safety are still being investigated. This review provides an overview of endothelin biology and the clinical use of ERAs for the treatment of PAH. The use of ERAs for other forms of pulmonary hypertension will not be reviewed here.

KEYWORDS

Pulmonary hypertension - endothelin - bosentan - sitaxsentan

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Richard N ChannickM.D. 

Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California

San Diego, 9300 Campus Point Dr., MC 7381

La Jolla, CA 92037

Email: rchannick@ucsd.edu