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The science of endothelin‐1 and endothelin receptor antagonists in the management of pulmonary arterial hypertension: current understanding and future studies
Author(s) -
Davie N. J.,
Schermuly R. T.,
Weissmann N.,
Grimminger F.,
Ghofrani H. A.
Publication year - 2009
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2009.02120.x
Subject(s) - endothelin receptor , medicine , pulmonary hypertension , receptor , endothelin 1 , pathological , vascular disease , endothelial dysfunction , pathophysiology of hypertension , blockade , cardiology , pharmacology , blood pressure
Pathological vascular remodelling is a key contributor to the symptomatology of pulmonary arterial hypertension (PAH), and reversing this process may offer the best hope for improving this debilitating condition. The vascular remodelling process is believed to be due to endothelial cell dysfunction and to involve altered production of endothelial cell‐derived vasoactive mediators. The observation that circulating plasma levels of the vasoactive peptide endothelin (ET)‐1 are raised in patients with PAH, and that ET‐1 production is increased in the pulmonary tissue of affected individuals, makes it a particularly interesting target for a therapeutic intervention in PAH. Clinical trials with ET receptor antagonists (ETRAs) show that they provide symptomatic benefit in patients with PAH, thereby proving the clinical relevance of the ET system as a therapeutic target. In this paper, we review the role of ET‐1 together with the available data on the roles of the specific ET receptors and ETRAs in PAH. In particular, we discuss the possible role of ET receptor selectivity in the vascular remodelling process in PAH and whether selective ET A or nonselective ET A /ET B blockade offers the greatest potential to improve symptoms and alter the clinical course of the disease.