title: Association of ex vivo vascular and bronchial dysfunctions in smokers.
abstract: BACKGROUND
  It has recently been shown that systemic endothelial dysfunction is associated with airflow limitation in COPD. We conducted this ex vivo study to assess whether endothelial dysfunction of pulmonary arteries of former smokers was associated with modifications of airway functions.
  
  
  METHODS
  Pharmacological experiments were conducted on arterial and bronchial rings obtained from lung specimen of 20 patients: 13 smokers without COPD and 7 smokers with mild to moderate COPD (GOLD class I or II). The impairment of acetylcholine-mediated vasodilation (constriction) of preconstricted arterial rings defined endothelial dysfunction. Resting tone (initial and after a contraction test) and cGMP-mediated dilation of bronchial rings in response to zaprinast were evaluated.
  
  
  RESULTS
  Initial airway resting tone was correlated with airflow limitation (FEV(1) % predicted: Rho = -0.49; p = 0.032). The acetylcholine response of arterial rings was correlated with zaprinast-induced bronchodilation (Rho = 0.54, p = 0.019). Patients with endothelial dysfunction (n = 5), as compared with those displaying no dysfunction (n = 15), were characterized by an increased resting tone (after contraction test), an impaired response to zaprinast but a similar degree of airflow limitation (FEV(1)).
  
  
  CONCLUSIONS
  Endothelial dysfunction of pulmonary arteries is associated with increased resting tone and impaired cGMP-mediated dilation of airways in former smokers, suggesting common underlying mechanisms of pulmonary arterial and bronchial dysfunctions.
authors.affiliation: Université Paris Descartes, UFR Biomédicale des Saints-Pères, UPRES EA 4068, Paris, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Oualha
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Boitiaux
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tadié
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cazes
authors.forename: Marc
authors.initials: M
authors.lastname: Riquet
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Naline
authors.forename: Dominique
authors.initials: D
authors.lastname: Israël-Biet
authors.forename: Christophe
authors.initials: C
authors.lastname: Delclaux
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001980:Bronchi / Q000187:drug effects / Q000473:pathology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D011688:Purinones / Q000494:pharmacology; D012907:Smoking / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D011688:Purinones; C011145:zaprinast; D006152:Cyclic GMP; D000109:Acetylcholine