title: Hemodynamic stresses induce endothelial dysfunction and remodeling of pulmonary artery in experimental compensated heart failure.
abstract: BACKGROUND
  We hypothesized that, in compensated heart failure (HF), hemodynamic perturbations and their consequences exist in pulmonary artery (PA) despite the absence of any perturbation in thoracic aorta (TA).
  
  
  RESULTS
  The left coronary artery was ligated in 20 male Wistar rats with compensated HF. Four months after ligation, these rats were compared with 20 sham-operated control rats. Blood pressure, velocity, viscosity, luminal diameter, and wall tensile and shear stresses were determined in PA and TA. Arterial rings were mounted in a myograph for ex vivo study. Endothelial nitric oxide synthase (eNOS) mRNA expression was determined in lung and aorta. Sections of PA and TA were used for histomorphometric study. In PA from rats with compensated HF, (1) blood pressure and wall tensile stress increased, whereas blood velocity and wall shear stress decreased; (2) contractions to KCl were not altered, but maximal contraction to phenylephrine and EC(50) decreased; (3) endothelium-dependent relaxation to acetylcholine and basal NO activity were blunted, whereas endothelium-independent relaxation was preserved; (4) eNOS mRNA levels and eNOS transcription in lung nuclei decreased; and (5) medial cross-sectional area, thickness, smooth muscle cell number, elastin, and collagen contents increased. Conversely, no such changes were found in TA from rats with compensated HF.
  
  
  CONCLUSIONS
  In compensated HF induced by small myocardial infarction, hemodynamics, vascular wall function, and structure are altered in PA but preserved in TA. These results indicate that the pulmonary vascular bed is an early target of regional circulatory alterations in HF.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unit 141 Hôpital Lariboisière, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Ben Driss
authors.forename: C
authors.initials: C
authors.lastname: Devaux
authors.forename: D
authors.initials: D
authors.lastname: Henrion
authors.forename: M
authors.initials: M
authors.lastname: Duriez
authors.forename: C
authors.initials: C
authors.lastname: Thuillez
authors.forename: B I
authors.initials: BI
authors.lastname: Levy
authors.forename: J B
authors.initials: JB
authors.lastname: Michel
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology*; D002302:Cardiac Output; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000473:pathology* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D011651:Pulmonary Artery / Q000473:pathology* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left
chemical_list: D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat