Dept of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Dept of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Respiratorias, Madrid, Spain.
Eur Respir J. 2015 Aug;46(2):346-54. doi: 10.1183/09031936.00139914. Epub 2015 Apr 30.
Sildenafil, a phosphodiesterase-5 inhibitor used to treat pulmonary hypertension, may have effects on pulmonary vessel structure and function. We evaluated the effects of sildenafil in a cigarette smoke (CS)-exposed model of chronic obstructive pulmonary disease (COPD).42 guinea-pigs were exposed to cigarette smoke or sham-exposed and treated with sildenafil or vehicle for 12 weeks, divided into four groups. Assessments included respiratory resistance, pulmonary artery pressure (PAP), right ventricle (RV) hypertrophy, endothelial function of the pulmonary artery and lung vessel and parenchymal morphometry.CS-exposed animals showed increased PAP, RV hypertrophy, raised respiratory resistance, airspace enlargement and intrapulmonary vessel remodelling. CS exposure also produced wall thickening, increased contractility and endothelial dysfunction in the main pulmonary artery. CS-exposed animals treated with sildenafil showed lower PAP and a trend to less RV hypertrophy than CS-exposed only animals. Furthermore, sildenafil preserved the intrapulmonary vessel density and attenuated the airspace enlargement induced by CS. No differences in gas exchange, respiratory resistance, endothelial function and vessel remodelling were observed.We conclude that in this experimental model of COPD, sildenafil prevents the development of pulmonary hypertension and contributes to preserve the parenchymal and vascular integrity, reinforcing the notion that the nitric oxide-cyclic guanosine monophosphate axis is perturbed by CS exposure.
西地那非是一种磷酸二酯酶-5 抑制剂，用于治疗肺动脉高压，可能对肺血管结构和功能有影响。我们在慢性阻塞性肺疾病（COPD）的香烟烟雾（CS）暴露模型中评估了西地那非的作用。42 只豚鼠暴露于香烟烟雾或假暴露，并接受西地那非或载体治疗 12 周，分为四组。评估包括呼吸阻力、肺动脉压（PAP）、右心室（RV）肥大、肺动脉内皮功能和肺血管及实质形态计量学。CS 暴露的动物表现出 PAP 升高、RV 肥大、呼吸阻力升高、气腔扩大和肺内血管重塑。CS 暴露还导致主肺动脉壁增厚、收缩力增加和内皮功能障碍。与仅 CS 暴露的动物相比，接受西地那非治疗的 CS 暴露动物的 PAP 较低，RV 肥大趋势较小。此外，西地那非保留了肺内血管密度，并减轻了 CS 引起的气腔扩大。在气体交换、呼吸阻力、内皮功能和血管重塑方面没有观察到差异。我们得出结论，在 COPD 的这个实验模型中，西地那非可预防肺动脉高压的发生，并有助于维持肺实质和血管的完整性，进一步证明了 CS 暴露会干扰一氧化氮-环磷酸鸟苷轴的观点。
