Optimizing endothelin receptor antagonist use in the management of pulmonary arterial hypertension

Abstract

Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientifi c research has shown that endothelin-1 (ET-1) is overexpressed in several forms of pulmonary vascular disease and may play an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) improved exercise capacity, functional status, pulmonary hemodymanics, and delayed the time to clinical worsening in several randomized placebocontrolled trials. Two ERAs are currently approved by the US Food and Drug Administration: bosentan, a dual ERA for patients with class III and IV PAH, and ambrisentan, a selective ERA for patients with class II and III PAH. Sitaxsentan, another selective ERA, has been approved in Europe, Canada, and Australia. The objective of this review is to evaluate the available evidence describing the pharmacology, effi cacy, safety, and tolerability, and patient-focused perspectives regarding the different types of endothelin receptor antagonists. Ongoing and forthcoming randomized trials are also highlighted including the approach of combining this class of drugs with other drugs that target different cellular pathways believed to be etiologically important in PAH.

Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

“…Our data on uterine artery are in line with studies performed on myometrial resistance arteries also showing a partial inhibition of ET-1 induced contraction though contraction is more pronounced in preeclamptic specimen [31] . Besides the fact that they are considered teratogenic [32] and contraindicated in pregnancy [33] , ERAs are not expected to do better than Ca 2+ antagonists.…”