Pulmonary Arterial Hypertension: Role of Ambrisentan

Increasing numbers of experimental investigations and recently also of clinical trials strongly suggest an integral involvement of the endothelin (ET) system in the pathophysiology of a variety of disease states, mainly of the cardiovascular system.Ambrisentan (LU 208075)approved by the US Food and Drug Administration in 2007, a selective ETA-receptor antagonist, is an orally active diphenyl propionic acid derivative that was recently approved for treatment of pulmonary arterial hypertension (PAH) in patients with World Health Organization class II or III symptoms.. It has been shown to have a very promising efficacy to safety ratio in the initial clinical trials. Phase II and Phase III trials with ambrisentan in pulmonary arterial hypertension have been performed. Pulmonary arterial hypertension (PAH) is a rare and progressive disease of the pulmonary arterial circulation that is characterized by a progressive rise in pulmonary vascular resistance, eventually leading to right-heart failure and death. Endothelin (ET) is a potent vasoconstrictor with mitogenic, hypertrophic and pro-inflammatory properties. Therefore, blockade of ET receptors has been suggested as an attractive target in a number of acute and chronic cardiovascular indications, including pulmonary arterial hypertension (PAH), systemic hypertension, and heart failure. In Phase III clinical trials in patients with PAH, ambrisentan (2.5–10 mg orally once-daily) improved exercise capacity, time to clinical worsening, WHO functional class, and quality of life compared with placebo. This review discusses the endothelin family of proteins and receptors and their role in the pathophysiology of pulmonary hypertensive diseases.