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.

CONCLUSION:

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: Dominik Linz, Mathias Hohl, Felix Mahfoud, Jan-Christian Reil, Wolfgang Linz, Thomas Hübschle, Hans-Paul Juretschke, Claudia Neumann-Häflin, Hartmut Rütten, Michael Böhm
• Journal: Journal of translational medicine (J Transl Med) Vol. 10 Pg. 187 (Sep 10 2012) ISSN: 1479-5876 [Electronic] England
• PMID: 22963383 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Calcium

Topics

• Animals
• Blood Pressure
• Calcium (metabolism)
• Gene Expression Profiling
• Hemodynamics
• Magnetic Resonance Imaging
• Male
• Obesity (complications, physiopathology)
• Rats
• Rats, Inbred SHR
• Ventricular Dysfunction, Left (complications, genetics, physiopathology)
• Ventricular Remodeling (genetics)