title: Cardiac remodeling and diastolic dysfunction in DahlS.Z-Lepr(fa)/Lepr(fa) rats: a new animal model of metabolic syndrome.
abstract: We recently characterized male DahlS.Z-Lepr(fa)/Lepr(fa) (Dahl salt-sensitive (DS)/obese) rats, which were established from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome (MetS). We have now investigated cardiac pathophysiology and metabolic changes in female DS/obese rats in comparison with homozygous lean female littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean, rats). Animals were maintained on a normal diet and were subjected to echocardiography followed by various pathological analyses at 15 weeks of age. Systolic blood pressure was significantly higher in female DS/obese rats than in DS/lean females at 12 weeks of age and thereafter. The survival rate of DS/obese rats was significantly lower than that of DS/lean rats at 15 weeks. Body weight, as well as visceral and subcutaneous fat mass were significantly increased in DS/obese rats, which also manifested left ventricular (LV) diastolic dysfunction and marked LV hypertrophy and fibrosis. In addition, myocardial oxidative stress and inflammation were increased in DS/obese rats compared with DS/lean rats. Serum insulin and triglyceride levels as well as the ratio of low-density lipoprotein- to high-density lipoprotein-cholesterol levels were markedly elevated in DS/obese rats, whereas fasting serum glucose concentrations were similar in the two rat strains. The phenotype of female DS/obese rats is similar to that of MetS in humans. These animals also develop salt-sensitive hypertension and LV diastolic dysfunction as well as LV hypertrophy and fibrosis, and these changes are associated with increased cardiac oxidative stress and inflammation.
authors.affiliation: Department of Pathophysiology Laboratory Sciences, University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tamayo
authors.initials: T
authors.lastname: Murase
authors.forename: Takuya
authors.initials: T
authors.lastname: Hattori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ohtake
authors.forename: Mayuna
authors.initials: M
authors.lastname: Abe
authors.forename: Yui
authors.initials: Y
authors.lastname: Amakusa
authors.forename: Miwa
authors.initials: M
authors.lastname: Takatsu
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D048429:Cell Size; D003971:Diastole / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000502:physiology; D007150:Immunohistochemistry; D024821:Metabolic Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology*; D009205:Myocarditis / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000502:physiology; D009765:Obesity / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D020303:Rats, Inbred Dahl; D060888:Real-Time Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000235:genetics*; D013481:Superoxides / Q000378:metabolism; D013534:Survival; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D054411:Receptors, Leptin; D013481:Superoxides