Differential vasoactive response to endothelin receptor antagonists and prostacyclin in patients with severe pulmonary hypertension.

Pulmonary hypertension (PH) is a rare disease of the pulmonary vasculature with diverse pathogenetic mechanisms. Vasoactive substances such as endothelin A receptor (ET(A)) antagonists and prostanoids have been used to improve haemodynamics and clinical outcome. We compared the hemodynamic response to BQ-123 (an ET(A) receptor antagonist) and prostacyclin or its analogue iloprost in ten patients (four men) with a mean age of 35.9+/-15.6 years. Seven patients had primary PH and three had PH owing to connective tissue disease. Patients underwent haemodynamic evaluation before and after administration of intra-atrial BQ-123 (200 mmol/min for 60 min), intravenous prostacyclin (3 ng x kg(-1) x min(-1) for 4 h) or iloprost as an aerosol (100 microg over 24 h). Response to vasodilator administration was defined as >15% decrease in pulmonary vascular resistance index (PVRI). Of the ten patients, five showed a response to BQ-123 and eight responded to prostanoids. Four patients were responders and one patient was a non-responder to both agents. PVRI decreased by 16.6+/-13.4% with BQ-123, and 24.4+/-15.7% with prostanoids (not statistically significant). The aetiology of PH did not affect the response to either drug. In conclusion, response to ET(A) antagonist or prostanoid administration can be achieved in a large group of patients with severe PH, however few patients respond identically to both agents. These findings are consistent with a multifactorial mechanism involved in this disease.