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Effects of cigarette smoke on endothelial function of pulmonary arteries in the guinea pig
- Source :
- Recercat. Dipósit de la Recerca de Catalunya, instname, Dipòsit Digital de la UB, Universidad de Barcelona, Respiratory Research, Respiratory Research, Vol 10, Iss 1, p 76 (2009)
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
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 α-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.
- Subjects :
- Male
Pathology
Time Factors
Vasodilator Agents
Vasodilation
Muscle, Smooth, Vascular
Desmin
Smoke
Vasoconstrictor Agents
Cigarette smokers
Fumadors
Endothelial dysfunction
Lung
Malalties pulmonars obstructives cròniques
Inhalation Exposure
Reverse Transcriptase Polymerase Chain Reaction
Smoking
Cell Differentiation
Immunohistochemistry
medicine.anatomical_structure
Pulmonary Emphysema
medicine.symptom
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Nitric Oxide Synthase Type III
Endothelium
Guinea Pigs
Down-Regulation
Pulmonary Artery
Conills porquins
medicine.artery
medicine
Animals
RNA, Messenger
Chronic obstructive pulmonary diseases
Cell Proliferation
lcsh:RC705-779
Aorta
Dose-Response Relationship, Drug
business.industry
Research
lcsh:Diseases of the respiratory system
medicine.disease
Pulmonary hypertension
Actins
Pulmonary Alveoli
Vasoconstriction
Pulmonary artery
Guinea pigs
Endothelium, Vascular
business
Subjects
Details
- ISSN :
- 1465993X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Respiratory Research
- Accession number :
- edsair.doi.dedup.....570a59d4fff2fc59f9e240252ae90a64