title: Interactions among vascular-tone modulators contribute to high altitude pulmonary edema and augmented vasoreactivity in highlanders.
abstract: BACKGROUND
  The interactions among various biomarkers remained unexplored under the stressful environment of high-altitude. Present study evaluated interactions among biomarkers to study susceptibility for high altitude pulmonary edema (HAPE) in HAPE-patients (HAPE-p) and adaptation in highland natives (HLs); both in comparison to HAPE-free sojourners (HAPE-f).
  
  
  RESULTS
  All the subjects were recruited at 3500 m. We measured clinical parameters, biochemical levels in plasma and gene expression using RNA from blood; analyzed various correlations between and among the clinical parameters, especially arterial oxygen saturation (SaO(2)) and mean arterial pressure (MAP) and biochemical parameters like, asymmetric dimethylarginine (ADMA), serotonin (5-HT), 8-iso-prostaglandin F2α (8-isoPGF2α), endothelin-1 (ET-1), plasma renin activity (PRA), plasma aldosterone concentration (PAC), superoxide dismutase (SOD) and nitric oxide (NO) in HAPE-p, HAPE-f and HLs. ADMA, 5-HT, 8-isoPGF2α, ET-1 levels, and PAC were significantly higher (p<0.0001, each), whereas SOD activity and NO level were significantly lower in HAPE-p than HAPE-f (p ≤ 0.001). Furthermore, ADMA, 5-HT, 8-isoPGF2α, NO levels and PAC were significantly higher (p<0.0001), whereas ET-1 level significantly (p<0.0001) and SOD activity non-significantly (p>0.05) lower in HLs than HAPE-f. The expression of respective genes differed in the three groups. In the correlations, SaO(2) inversely correlated with ADMA, 5-HT and 8-isoPGF2α and positively with SOD in HAPE-p (p≤0.009). MAP correlated positively with 5-HT and 8-isoPGF2α in HAPE-p and HLs (p ≤ 0.004). A strong positive correlation was observed between ADMA and 5-HT, 5-HT and 8-isoPGF2α (p≤0.001), whereas inverse correlation of SOD with ET-1 in HAPE-p and HLs (p ≤ 0.004), with 5-HT and 8-isoPGF2α in HAPE-p (p = 0.01) and with 5-HT in HLs (p = 0.05).
  
  
  CONCLUSIONS
  The interactions among these markers confer enhanced vascular activity in HLs and HAPE in sojourners.
authors.affiliation: Institute of Genomics and Integrative Biology, Delhi, India.
authors.forename: Zahara
authors.initials: Z
authors.lastname: Ali
authors.forename: Aastha
authors.initials: A
authors.lastname: Mishra
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.forename: Perwez
authors.initials: P
authors.lastname: Alam
authors.forename: Priyanka
authors.initials: P
authors.lastname: Pandey
authors.forename: Rekhbala
authors.initials: R
authors.lastname: Ram
authors.forename: Tashi
authors.initials: T
authors.lastname: Thinlas
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mohammad
authors.forename: M A Qadar
authors.initials: MA
authors.lastname: Pasha
mesh_terms: D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood*; D001808:Blood Vessels / Q000503:physiopathology*; D005786:Gene Expression Regulation; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D000860:Hypoxia / Q000097:blood / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers