title: Changes in cardiac structure in hypertension produced by placental ischemia in pregnant rats: effect of tumor necrosis factor blockade.
abstract: OBJECTIVE
  Chronic reduction of uteroplacental perfusion pressure (RUPP) in pregnant rats leads to placental ischemia, maternal endothelial cell dysfunction, hypertension and elevated levels of tumor necrosis factor-alpha (TNF-α). In this study we investigated the hypothesis that placental ischemia in pregnant rat, a model of preeclampsia, stimulates cardiac hypertrophy and fibrosis via a TNF-α-dependent mechanism.
  
  
  METHODS
  Normal pregnant Sprague-Dawley rats and RUPP rats were evaluated on day 19 of gestation. To test the role of TNF-α in mediating change in the RUPP rat heart, a TNF-α inhibitor, etanercept, was administered on day 18 of gestation at a dose of 0.8 mg/kg, s.c.
  
  
  RESULTS
  In comparison to normal pregnant rats, RUPP animals display enlarged cardiomyocytes, microvascular rarefaction, fibrosis, apoptosis as well as increased expression of markers of heart hypertrophy and fibrosis. Etanercept (E) treatment prevented enlargement of cardiomyocytes, fibrosis and apoptosis and this was accompanied by significantly lowered blood pressure in RUPP rats. Etanercept treatment lowered expression of mRNA for brain natriuretic peptide, a marker of cardiac hypertrophy. It also heightened expression of endothelial nitric oxide synthase and its phosphorylation as well as oxytocin receptor identified in cardiac microvessels. TNF-α inhibition prevented microvascular rarefaction in the heart as indicated by augmented CD31, a marker of angiogenesis.
  
  
  CONCLUSIONS
  These results suggest that RUPP leads to microvascular rarefaction in the heart, exaggerated cardiomyocyte size, apoptosis, fibrosis, and the alteration of cardiac gene expression that are modulated by the inflammatory cytokine TNFα.
authors.affiliation: Laboratory of Cardiovascular Biochemistry, Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM)-Hôtel-Dieu, Montreal, Quebec, Canada. jolanta.gutkowska@umontreal.ca
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
authors.forename: Babbette B
authors.initials: BB
authors.lastname: Lamarca
authors.forename: Bogdan A
authors.initials: BA
authors.lastname: Danalache
authors.forename: Donghao
authors.initials: D
authors.lastname: Wang
authors.forename: Marek
authors.initials: M
authors.lastname: Jankowski
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006973:Hypertension / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D010920:Placenta / Q000098:blood supply*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D052250:Nitric Oxide Synthase Type III