Endothelin and Its Blockade in Pulmonary Arterial Hypertension

TL;DRAbstract

Endothelin-1, a potent vasoconstrictor and mitogenic peptide manufactured by endothelial cells, has been identified as an important mediator in human pulmonary arterial hypertension. Endothelin-1 binds to two different receptors, termed ETA and ETB. While it is generally agreed that the ETA receptor is the predominant receptor responsible for constriction and proliferation, it is unclear whether the net effect of ETB-receptor activation is beneficial or detrimental. In the past decade, the development of both nonspecific and specific ETA endothelin-receptor antagonists has offered hope of benefit for patients with PAH. These agents have the advantage of permitting oral administration with once- or twice-daily dosing. They improve functional status and capacity as well as pulmonary hemodynamics and slow the time to clinical worsening. Elevation of liver enzymes appears to be a class effect, although some agents may be less liver-toxic than others. However, many questions remain to be an

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