Sildenafil in a cigarette smoke-induced model of COPD in the guinea-pig.
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.
Dept of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
David
D
Domínguez-Fandos
Dept of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
César
C
Valdés
Dept of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Elisabet
E
Ferrer
Dept of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Raquel
R
Puig-Pey
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.
Isabel
I
Blanco
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.
Olga
O
Tura-Ceide
Dept of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Tanja
T
Paul
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.
Víctor I
VI
Peinado
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 jbarbera@clinic.ub.es.
Joan A
JA
Barberà
D000818:Animals; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000209:etiology; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D058986:Phosphodiesterase 5 Inhibitors; D014028:Tobacco Smoke Pollution; D000068677:Sildenafil Citrate