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Endothelin receptor antagonists in pulmonary arterial hypertension

¹ Research Center of the Montreal Heart Institute, ² Dept of Medicine, University of Montreal, Montreal, QC, Canada, and ³ Dept of Respiratory Medicine, Hanover Medical School, Hanover, Germany.

CORRESPONDENCE: M. M. Hoeper, Dept of Respiratory Medicine, Hannover Medical School, 30623 Hannover, Germany. Fax: 49 5115328536. E-mail: hoeper.marius{at}mh-hannover.de

Keywords: Endothelin, endothelin receptor antagonists, hypertension, pulmonary

Received: June 26, 2007
Accepted August 29, 2007

The endothelin (ET) system, especially ET-1 and the ET_A and ET_B receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH.

Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET_A and ET_B receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET_A receptor.

There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs.

For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients.

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