title: Systemic oxidative stress and endothelial dysfunction is associated with an attenuated acute vascular response to inhaled prostanoid in pulmonary artery hypertension patients.
abstract: BACKGROUND
  Systemic endothelial dysfunction and increased oxidative stress have been observed in pulmonary arterial hypertension (PAH). We evaluate whether oxidative stress and endothelial dysfunction are associated with acute pulmonary vascular bed response to an inhaled prostanoid in PAH patients.
  
  
  METHODS
  Fourteen idiopathic PAH patients and 14 controls were included. Oxidative stress was assessed through plasma malondialdehyde (MDA) levels and xanthine oxidase (XO) and endothelial-bound superoxide dismutase (eSOD) activity. Brachial artery endothelial-dependent flow-mediated vasodilation (FMD) was used to evaluate endothelial function. Hemodynamic response to inhaled iloprost was assessed with transthoracic echocardiography.
  
  
  RESULTS
  PAH patients showed impaired FMD (2.8 ± 0.6 vs. 10.7 ± 0.6%, P < .01), increased MDA levels and XO activity (0.6 ± 0.2 vs. 0.3 ± 0.2 μM, P < .01 and 0.04 ± 0.01 vs. 0.03 ± 0.01 U/mL, P = .02, respectively) and decreased eSOD activity (235 ± 23 vs. 461 ± 33 AUC, P < .01). Iloprost improved right cardiac output (3.7 ± 0.6 to 4.1 ± 1.2 L/min, P = .02) and decreased pulmonary vascular resistance (4.1 ± 1.1 to 2.9 ± 0.9 Wood U, P = .01). Changes in right cardiac output after prostanoid inhalation correlated significantly with baseline eSOD activity and FMD (Rho: 0.61, P < .01 and Rho: 0.63, P = .01, respectively).
  
  
  CONCLUSIONS
  PAH patients show increased systemic oxidative stress and endothelial dysfunction markers. Response to inhaled prostanoid is inversely related to both parameters.
authors: Departamento Enfermedades Cardiovasculares, Facultad de Medicina, Santiago, Chile.
authors: Luigi A
authors: LA
authors: Gabrielli
authors: Pablo F
authors: PF
authors: Castro
authors: Ivan
authors: I
authors: Godoy
authors: Rosemarie
authors: R
authors: Mellado
authors: Robert C
authors: RC
authors: Bourge
authors: Hernan
authors: H
authors: Alcaino
authors: Mario
authors: M
authors: Chiong
authors: Douglas
authors: D
authors: Greig
authors: Hugo E
authors: HE
authors: Verdejo
authors: Mario
authors: M
authors: Navarro
authors: Rafael
authors: R
authors: Lopez
authors: Barbra
authors: B
authors: Toro
authors: Clara
authors: C
authors: Quiroga
authors: Guillermo
authors: G
authors: Díaz-Araya
authors: Sergio
authors: S
authors: Lavandero
authors: Lorena
authors: L
authors: Garcia
mesh_terms: D000208:Acute Disease; D000280:Administration, Inhalation; D000328:Adult; D015415:Biomarkers; D001916:Brachial Artery / Q000187:drug effects; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D011453:Prostaglandins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects; D013482:Superoxide Dismutase / Q000097:blood; D014969:Xanthine Oxidase / Q000097:blood
chemical_list: D015415:Biomarkers; D011453:Prostaglandins; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase