title: SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction.
abstract: The SU5416 combined with hypoxia (SuHx) rat model features angio-obliterative pulmonary hypertension resembling human pulmonary arterial hypertension. Despite increasing use of this model, a comprehensive haemodynamic characterisation in conscious rats has not been reported. We used telemetry to characterise haemodynamic responses in SuHx rats and associated these with serial histology. Right ventricular systolic pressure (RVSP) increased to a mean±sd of 106±7 mmHg in response to SuHx and decreased but remained elevated at 72±8 mmHg upon return to normoxia. Hypoxia-only exposed rats showed a similar initial increase in RVSP, a lower maximum RVSP and near-normalisation of RVSP during subsequent normoxia. Progressive vascular remodelling consisted of a four-fold increase in intima thickness, while only minimal changes in media thickness were found. The circadian range in RVSP provided an accurate longitudinal estimate of vascular remodelling. In conclusion, in SuHx rats, re-exposure to normoxia leads to a partial decrease in pulmonary artery pressure, with persisting hypertension and pulmonary vascular remodelling characterised by progressive intima obstruction.
authors.affiliation: Dept of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: Michiel Alexander
authors.initials: MA
authors.lastname: de Raaf
authors.affiliation: Dept of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schalij
authors.affiliation: Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Gomez-Arroyo
authors.affiliation: Dept of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: Nina
authors.initials: N
authors.lastname: Rol
authors.affiliation: Dept of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Happé
authors.affiliation: Dept of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands Dept of Physiology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
authors.affiliation: Dept of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
authors.affiliation: Dept of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands Dept of Physiology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Westerhof
authors.affiliation: Pulmonary and Critical Care Medicine Division, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Voelkel
authors.affiliation: Dept of Pulmonology, VU University Medical Center/Institute for Cardiovascular Research, Amsterdam, The Netherlands HJ.Bogaard@vumc.nl.
authors.forename: Harm Jan
authors.initials: HJ
authors.lastname: Bogaard
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry; D000818:Animals; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D018450:Disease Progression; D004452:Echocardiography; D006352:Heart Ventricles / Q000473:pathology; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D007211:Indoles / Q000737:chemistry*; D008168:Lung / Q000503:physiopathology; D008297:Male; D011651:Pulmonary Artery / Q000473:pathology; D011758:Pyrroles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole; D013686:Telemetry; D017539:Tunica Intima / Q000473:pathology*; D066253:Vascular Remodeling
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; C116890:Semaxinib