Endothelin receptor antagonism in portal hypertension

Endothelin receptor antagonists (ERAs) have recently become prominent therapies for pulmonary arterial hypertension, and are being explored clinically in several areas, including resistant hypertension, idiopathic pulmonary fibrosis, and cancer.

To review the available preclinical and clinical data surrounding ERAs and their potential role to treat portal hypertension.

A systematic search of peer-reviewed publications was performed using PubMed and Ovid/Medline/EMBASE databases.

Several preclinical in vivo studies have evaluated ERAs in models of portal hypertension. The majority of these studies employ nonselective ERAs, and support the hypothesis that endothelin participates in the development and maintenance of portal hypertension. A limited number of studies have addressed whether ET(A) receptor-selective ERAs provide an advantage over nonselective agents in ameliorating the effects of portal hypertension, and the majority of these data indicate that selective ERAs may be sufficient. Very few clinical studies have evaluated ERAs in portal hypertension patients. What has been described in humans supports a role for endothelin, but is not sufficient to draw conclusions regarding ERA selectivity.

While preclinical evidence suggests a role for endothelin and ERAs in portal hypertension, scant and equivocal clinical data highlight a need for human studies with current selective and nonselective ERAs.