title: Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats.
abstract: BACKGROUND
  The additive effects of obesity and metabolic syndrome on left ventricular (LV) maladaptive remodeling and function in hypertension are not characterized.
  
  
  METHODS
  We compared an obese spontaneously hypertensive rat model (SHR-ob) with lean spontaneously hypertensive rats (SHR-lean) and normotensive controls (Ctr). LV-function was investigated by cardiac magnetic resonance imaging and invasive LV-pressure measurements. LV-interstitial fibrosis was quantified and protein levels of phospholamban (PLB), Serca2a and glucose transporters (GLUT1 and GLUT4) were determined by immunohistochemistry.
  
  
  RESULTS
  Systolic blood pressure was similar in SHR-lean and SHR-ob (252 ± 7 vs. 242 ± 7 mmHg, p = 0.398) but was higher when compared to Ctr (155 ± 2 mmHg, p < 0.01 for both). Compared to SHR-lean and Ctr, SHR-ob showed impaired glucose tolerance and increased body-weight. In SHR-ob, LV-ejection fraction was impaired vs. Ctr (46.2 ± 1.1 vs. 59.6 ± 1.9%, p = 0.007). LV-enddiastolic pressure was more increased in SHR-ob than in SHR-lean (21.5 ± 4.1 vs. 5.9 ± 0.81 mmHg, p = 0.0002) when compared to Ctr (4.3 ± 1.1 mmHg, p < 0.0001 for both), respectively. Increased LV-fibrosis together with increased myocyte diameters and ANF gene expression in SHR-ob were associated with increased GLUT1-protein levels in SHR-ob suggestive for an upregulation of the GLUT1/ANF-axis. Serca2a-protein levels were decreased in SHR-lean but not altered in SHR-ob compared to Ctr. PLB-phosphorylation was not altered.
  
  
  CONCLUSIONS
  In addition to hypertension alone, metabolic syndrome and obesity adds to the myocardial phenotype by aggravating diastolic dysfunction and a progression towards systolic dysfunction. SHR-ob may be a useful model to develop new interventional and pharmacological treatment strategies for hypertensive heart disease and metabolic disorders.
authors.affiliation: Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg/Saar 66421, Germany. dominik.linz@uks.eu
authors.forename: Dominik
authors.initials: D
authors.lastname: Linz
authors.forename: Mathias
authors.initials: M
authors.lastname: Hohl
authors.forename: Felix
authors.initials: F
authors.lastname: Mahfoud
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Reil
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Linz
authors.forename: Thomas
authors.initials: T
authors.lastname: Hübschle
authors.forename: Hans-Paul
authors.initials: HP
authors.lastname: Juretschke
authors.forename: Claudia
authors.initials: C
authors.lastname: Neumann-Häflin
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rütten
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D020869:Gene Expression Profiling; D006439:Hemodynamics; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D018487:Ventricular Dysfunction, Left / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D002118:Calcium