title: Early increase in pulmonary vascular reactivity with overexpression of endothelin-1 and vascular endothelial growth factor in canine experimental heart failure.
abstract: Heart failure is a cause of pulmonary vasoconstriction and remodelling, leading to pulmonary hypertension (PH) and decreased survival. The pathobiology of PH in heart failure remains incompletely understood. We investigated pulmonary vascular function and signalling molecules in early stage PH secondary to experimental heart failure. Eight beagle dogs with overpacing-induced heart failure underwent haemodynamic assessment and postmortem pulmonary arterial reactivity, morphometry and quantification of genes encoding for factors involved in vascular reactivity and remodelling: endothelin-1 (ET-1), ETA and ETB receptors, vascular endothelial growth factor (VEGF), VEGF receptors 1 and 2 (VEGFR1 and VEGFR2), endothelial nitric oxide synthase, angiopoietin-1, bone morphogenetic protein receptors (BMPR1A and BMPR2), serotonin transporter (5-HTT) and the 5-HT(2B) receptor. Overpacing was associated with a decrease in cardiac output and an increase in pulmonary vascular pressures. However, there were no changes in pulmonary vascular resistance or in arteriolar medial thickness. There were increased expressions of genes encoding for ET-1, ETB, VEGF and VEGFR2, while expression of the other genes analysed remained unchanged. In vitro, pulmonary arteries showed decreased relaxation and increased reactivity, while systemic mammary arteries were unaffected. Early PH in heart failure is characterized by altered vasoreactivity and increased ET-1/ETB and VEGF/VEGFR2 signalling.
authors.affiliation: Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Erasme Campus CP 604, 808 Lennik Road, B-1070 Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Ray
authors.forename: M
authors.initials: M
authors.lastname: Mathieu
authors.forename: P
authors.initials: P
authors.lastname: Jespers
authors.forename: I
authors.initials: I
authors.lastname: Hadad
authors.forename: M
authors.initials: M
authors.lastname: Mahmoudabady
authors.forename: A
authors.initials: A
authors.lastname: Pensis
authors.forename: S
authors.initials: S
authors.lastname: Motte
authors.forename: I R
authors.initials: IR
authors.lastname: Peters
authors.forename: R
authors.initials: R
authors.lastname: Naeije
authors.forename: K
authors.initials: K
authors.lastname: McEntee
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D006333:Heart Failure / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016133:Polymerase Chain Reaction; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011652:Pulmonary Circulation; D044023:Receptor, Endothelin B / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014655:Vascular Resistance; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D019332:Endothelin-1; D044023:Receptor, Endothelin B; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2