Bosentan Reduces Pulmonary Artery Pressure in High Altitude Residents

Abstract

UNLABELLED: Endothelin-1 (ET-1) plays a critical role in the regulation of pulmonary vascular tone. The aim of this study was to investigate the role of ET-1 in the pathogenesis of high altitude pulmonary arterial hypertension (HAPH). METHODS: Pulmonary artery pressure (PAP) was measured by echocardiography in permanent residents of the Kyrgyz Republic (3200-4000 m above sea level) both before and 3 h after a single oral dose of ET receptor antagonist, bosentan (125 mg). Plasma ET-1 levels were measured by ELISA assay. Genomic DNA was extracted from peripheral blood samples and the frequency of -3a and -4a alleles of the ET-1 gene determined by PCR. RESULTS: Plasma ET-1 in HAPH highlanders was significantly higher than in healthy subjects (7.05±2.35 vs. 4.65±1.65 pg/ml, p<0.002). After the treatment with 125 mg bosentan, systolic PAP decreased from 46±1.9 to 37±2.2 mm Hg (p<0.01), and pulmonary artery acceleration time (PAAT) increased from 0.086±0.001 to 0.098±0.001 sec (p<0.001). The frequency of the -4a allele was significantly higher in HAPH patients compared to healthy highlanders (0.43 vs. 0.3, χ(2)=4.3, p=0.03). CONCLUSION: Increased ET-1 levels play an important role in development of HAPH.