Pulmonary Hypertension

Pulmonary hypertension (PH) is a complex cardiopulmonary disorder characterized by a mean pulmonary artery pressure (mPAP) greater than 20 mmHg at rest, as measured by right heart catheterization. The disease arises from multiple and interconnected mechanisms. Stimuli such as hypoxia and ischemia trigger increased expression and synthesis of endothelin (ET), which activates downstream signaling pathways that contribute to pathological changes, including abnormal vascular proliferation. This review examines the regulation of endothelin receptors and their associated pathways under both physiological and pathological conditions, highlighting the mechanistic actions of currently approved ET receptor antagonists used in clinical practice. Ongoing research focuses on developing multi-target therapeutic combinations and novel delivery strategies to enhance efficacy, improve patient adherence, and minimize adverse effects. Additionally, future directions emphasize precision medicine approaches and the potential of ET-targeted monotherapies to optimize treatment outcomes in PH.