title: Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig.
abstract: BACKGROUND
  Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease by altering the structure and function of pulmonary vessels at early disease stages. The objectives of this study were to evaluate the effects of long-term exposure to cigarette smoke on endothelial function and smooth muscle-cell proliferation in pulmonary arteries of guinea pigs.
  
  
  METHODS
  19 male Hartley guinea pigs were exposed to the smoke of 7 cigarettes/day, 5 days/week, for 3 and 6 months. 17 control guinea pigs were sham-exposed for the same periods. Endothelial function was evaluated in rings of pulmonary artery and aorta as the relaxation induced by ADP. The proliferation of smooth muscle cells and their phenotype in small pulmonary vessels were evaluated by immunohistochemical expression of alpha-actin and desmin. Vessel wall thickness, arteriolar muscularization and emphysema were assessed morphometrically. The expression of endothelial nitric oxide synthase (eNOS) was evaluated by Real Time-PCR.
  
  
  RESULTS
  Exposure to cigarette smoke reduced endothelium-dependent vasodilatation in pulmonary arteries (ANOVA p < 0.05) but not in the aorta. Endothelial dysfunction was apparent at 3 months of exposure and did not increase further after 6 months of exposure. Smoke-exposed animals showed proliferation of poorly differentiated smooth muscle cells in small vessels (p < 0.05) after 3 months of exposure. Prolonged exposure resulted in full muscularization of small pulmonary vessels (p < 0.05), wall thickening (p < 0.01) and increased contractility of the main pulmonary artery (p < 0.05), and enlargement of the alveolar spaces. Lung expression of eNOS was decreased in animals exposed to cigarette smoke.
  
  
  CONCLUSIONS
  In the guinea pig, exposure to cigarette smoke induces selective endothelial dysfunction in pulmonary arteries, smooth muscle cell proliferation in small pulmonary vessels and reduced lung expression of eNOS. These changes appear after 3 months of exposure and precede the development of pulmonary emphysema.
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-IDIBAPS, Barcelona, Spain. idib501@clinic.ub.es
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ferrer
authors.forename: Víctor Ivo
authors.initials: VI
authors.lastname: Peinado
authors.forename: Marta
authors.initials: M
authors.lastname: Díez
authors.forename: Josep Lluís
authors.initials: JL
authors.lastname: Carrasco
authors.forename: Melina Mara
authors.initials: MM
authors.lastname: Musri
authors.forename: Anna
authors.initials: A
authors.lastname: Martínez
authors.forename: Robert
authors.initials: R
authors.lastname: Rodríguez-Roisin
authors.forename: Joan Albert
authors.initials: JA
authors.lastname: Barberà
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003893:Desmin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006168:Guinea Pigs; D007150:Immunohistochemistry; D019570:Inhalation Exposure; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000199:Actins; D003893:Desmin; D012333:RNA, Messenger; D012906:Smoke; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D052250:Nitric Oxide Synthase Type III
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