title: Pulmonary artery remodeling differs in hypoxia- and monocrotaline-induced pulmonary hypertension.
abstract: In the present study we analyzed structural characteristics of muscular pulmonary arteries and arterioles in two classic models of pulmonary hypertension, the rat hypoxia and monocrotaline models. We hypothesized that an increase in medial cross-sectional area would result in reduction of the lumen area and that these parameters would correlate with the increase in pulmonary artery pressure (PAP). Four weeks after a single injection of monocrotaline (MCT) or after 4 wk of hypoxic exposure the rats were killed. Both MCT and chronic hypoxia induced right ventricular hypertrophy. In separate groups of rats both MCT and chronic hypoxia increased PAP. MCT increased the media cross-sectional area of pulmonary arteries with an external diameter between 30-100 microm and 101-200 microm and reduced the lumen area of pulmonary arteries with an external diameter between 101-200 microm. Chronic hypoxia only slightly increased the media cross-sectional area without a change of the lumen area. Both MCT and hypoxia increased the percentage of partly muscularized and muscularized arterioles. The angiotensin-converting enzyme (ACE) inhibitor captopril (0.5 mg/kg/h) had no effect on MCT-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary artery remodeling. In chronic hypoxic rats it prevented an increase in medial cross-sectional area of pulmonary arteries with an external diameter between 30-100 microm and attenuated the increase in the percentage of muscularized arterioles, without any effect on the PAP. We conclude that MCT, in contrast to chronic hypoxia, induces structural changes of muscular pulmonary arteries with an external diameter between 101-200 microm which may contribute to an increased PAP and right ventricular hypertrophy. These data also suggest that angiotensin II plays a pivotal role in remodeling of pulmonary arteries in hypoxia but not in MCT-induced pulmonary hypertension.
authors.affiliation: Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: van Suylen
authors.forename: J F
authors.initials: JF
authors.lastname: Smits
authors.forename: M J
authors.initials: MJ
authors.lastname: Daemen
mesh_terms: D000222:Adaptation, Physiological; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications*; D008297:Male; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D016686:Monocrotaline; D002216:Captopril