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
