Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig

Respir Res. 2009 Aug 14;10(1):76. doi: 10.1186/1465-9921-10-76.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Desmin / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Guinea Pigs
  • Immunohistochemistry
  • Inhalation Exposure
  • Lung / blood supply
  • Lung / drug effects*
  • Lung / enzymology
  • Lung / pathology
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Nitric Oxide Synthase Type III / genetics
  • Pulmonary Alveoli / drug effects
  • Pulmonary Alveoli / pathology
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology
  • Pulmonary Artery / physiopathology
  • Pulmonary Emphysema / chemically induced*
  • Pulmonary Emphysema / pathology
  • Pulmonary Emphysema / physiopathology
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoke / adverse effects*
  • Smoking / adverse effects*
  • Time Factors
  • Vasoconstriction / drug effects*
  • Vasoconstrictor Agents / pharmacology
  • Vasodilation / drug effects*
  • Vasodilator Agents / pharmacology


  • Actins
  • Desmin
  • RNA, Messenger
  • Smoke
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Nitric Oxide Synthase Type III