@misc{oai:u-fukui.repo.nii.ac.jp:00020231,
 author = {Kojonazarov, Baktybek and Isakova, Jainagul and Imanov, Bakytbek and Sovkhozova, Nurmira and Sooronbaev, Talantbek and Ishizaki, Takeshi and Aldashev, Almaz A.},
 month = {Oct},
 note = {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 (3200-4000m above sea level) both before and 3h after a single oral dose of ET receptor antagonist, bosentan (125mg). 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±1.65pg/ml, p<0.002). After the treatment with 125mg bosentan, systolic PAP decreased from 46±1.9 to 37±2.2mm 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, X2=4.3, p=0.03). Conclusion: Increased ET-1 levels play an important role in development of HAPH.},
 title = {Bosentan Reduces Pulmonary Artery Pressure in High Altitude Residents},
 year = {2012}
}