Department of Pulmonary Medicine, Hospital Clínic-IDIBAPS, Barcelona, Spain.
Respir Res. 2009 Aug 14;10(1):76. doi: 10.1186/1465-9921-10-76.
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.
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.
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.
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.
吸烟可能通过改变早期肺部疾病阶段的肺血管结构和功能导致慢性阻塞性肺疾病中的肺动脉高压。本研究的目的是评估长期暴露于香烟烟雾对豚鼠肺动脉内皮功能和平滑肌细胞增殖的影响。
19 只雄性 Hartley 豚鼠每天暴露于 7 支香烟的烟雾中，每周 5 天，暴露 3 个月和 6 个月。17 只对照豚鼠进行相同时间的假暴露。通过 ADP 诱导的松弛来评估肺血管和主动脉环的内皮功能。通过免疫组织化学表达α-肌动蛋白和结蛋白评估小肺动脉平滑肌细胞的增殖及其表型。通过形态计量学评估血管壁厚度、小动脉肌化和肺气肿。通过实时 PCR 评估内皮型一氧化氮合酶 (eNOS) 的表达。
暴露于香烟烟雾降低了肺血管的内皮依赖性血管舒张（ANOVA p < 0.05），但对主动脉无影响。暴露 3 个月后出现内皮功能障碍，6 个月后进一步增加。暴露于烟雾的动物在暴露 3 个月后在小血管中显示出分化不良的平滑肌细胞增殖（p < 0.05）。长时间暴露导致小肺动脉完全肌化（p < 0.05）、壁增厚（p < 0.01）和主肺动脉收缩力增加（p < 0.05）以及肺泡空间增大。暴露于香烟烟雾的动物肺中 eNOS 的表达降低。
在豚鼠中，暴露于香烟烟雾会导致肺血管选择性内皮功能障碍、小肺动脉平滑肌细胞增殖和肺中 eNOS 表达减少。这些变化在暴露 3 个月后出现，并先于肺气肿的发生。
