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This Article Full Text Full Text (PDF) All Versions of this Article: 93/3/434    most recent expphysiol.2007.040469v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ray, L. Articles by McEntee, K. PubMed PubMed Citation Articles by Ray, L. Articles by McEntee, K. Related Collections Vascular

¹ Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Brussels, Belgium ² Comparative Pathology, School of Clinical Veterinary Science, University of Bristol, Bristol, UK

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.

(Received 28 August 2007; accepted after revision 9 November 2007; first published online 9 November 2007)
Corresponding author K. McEntee: Laboratory of Physiology, Faculty of Medicine, Free University of Brussels, Erasme Campus CP 604, 808 Lennik Road, B-1070 Brussels, Belgium. Email: kmcentee{at}ulb.ac.be