ETB Receptor Antagonists

Targeting ETB receptors has provided important insights into their role in pulmonary hypertension (PH). Deletion or dysfunction of ETB receptors has been shown to accelerate disease progression and increase cellular and molecular markers associated with PH, highlighting their role in regulating basal pulmonary vascular tone and exerting anti-proliferative protective effects.

Experimental strategies have explored selective ETB antagonism to modulate PH. For example, cell-permeable peptides targeting ETB receptor fragments were developed to block ETB-mediated vasoconstriction in smooth muscle cells while preserving other receptor functions. These peptides inhibited ET-1–induced ERK and Akt phosphorylation in pulmonary artery smooth muscle cells, leading to reduced right ventricular (RV) systolic pressure, attenuated RV hypertrophy, and decreased fully muscularized pulmonary vessels, effectively alleviating PH symptoms.