Journal Article

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

Martínez, Anna, Carrasco, Josep Lluís, Rodríguez-Roisin, Robert, Peinado, Víctor Ivo, Albert Barberà, Joan, Musri, Melina Mara, Ferrer, Elisabet, Díez, Marta

2009

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Actins - metabolism / Analysis / Animals / Arteries / Cell Differentiation - drug effects / Cell Proliferation - drug effects / Chronic obstructive pulmonary diseases / Cigarette smokers / Conills porquins / Desmin - metabolism / Dose-Response Relationship, Drug / Down-Regulation / Endothelium / Endothelium, Vascular - drug effects / Endothelium, Vascular - physiopathology / Fumadors / Guinea Pigs / Health aspects / Immunohistochemistry / Inhalation Exposure / Lung - blood supply / Lung - drug effects / Lung - enzymology / Lung - pathology / Malalties pulmonars obstructives cròniques / Male / Medicine / Medicine & Public Health / Muscle proteins / Muscle, Smooth, Vascular - drug effects / Muscle, Smooth, Vascular - metabolism / Muscle, Smooth, Vascular - pathology / Nitric oxide / Nitric Oxide Synthase Type III - genetics / Physiological aspects / Pneumology/Respiratory System / Pulmonary Alveoli - drug effects / Pulmonary Alveoli - pathology / Pulmonary artery / Pulmonary Artery - drug effects / Pulmonary Artery - metabolism / Pulmonary Artery - pathology / Pulmonary Artery - physiopathology / Pulmonary Emphysema - chemically induced / Pulmonary Emphysema - pathology / Pulmonary Emphysema - physiopathology / Pulmonary hypertension / Respiratory tract diseases / Reverse Transcriptase Polymerase Chain Reaction / RNA, Messenger - metabolism / Smoke - adverse effects / Smoking / Smoking - adverse effects / Time Factors / Vasoconstriction - drug effects / Vasoconstrictor Agents - pharmacology / Vasodilation - drug effects / Vasodilator Agents - pharmacology