title: Bosentan reduces pulmonary artery pressure in high altitude residents.
abstract: 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).
  
  
  CONCLUSIONS
  Increased ET-1 levels play an important role in development of HAPH.
authors.affiliation: Institute of Molecular Biology and Medicine, Bishkek, Kyrgyzstan.
authors.forename: Baktybek
authors.initials: B
authors.lastname: Kojonazarov
authors.forename: Jainagul
authors.initials: J
authors.lastname: Isakova
authors.forename: Bakytbek
authors.initials: B
authors.lastname: Imanov
authors.forename: Nurmira
authors.initials: N
authors.lastname: Sovkhozova
authors.forename: Talantbek
authors.initials: T
authors.lastname: Sooronbaev
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Almaz A
authors.initials: AA
authors.lastname: Aldashev
mesh_terms: D000328:Adult; D000368:Aged; D000531:Altitude; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D016022:Case-Control Studies; D004452:Echocardiography; D019332:Endothelin-1 / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011651:Pulmonary Artery / Q000503:physiopathology; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D019332:Endothelin-1; D013449:Sulfonamides; D000077300:Bosentan