[Show abstract][Hide abstract] ABSTRACT: Abstract Kojonazarov, Baktybek, Jainagul Isakova, Baktybek Imanov, Nurmira Sovkhozova, Talantbek Sooronbaev, Takeshi Ishizaki, and Almaz A. Aldashev. Bosentan reduces pulmonary artery pressure in high altitude residents. High Alt Med Biol. 13:217-223, 2012.-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.
High altitude medicine & biology 09/2012; 13(3):217-23. · 1.58 Impact Factor