Establishment of a new animal model of metabolic syndrome: SHRSP fatty (fa/fa) rats

Hiraoka-Yamamoto, Junko; Nara, Yasuo; Yasui, Naomi; Onobayashi, Yuko; Tsuchikura, Satoru; Ikeda, Katsumi

doi:10.1111/j.1440-1681.2004.03962.x

Cited by 55 publications

(47 citation statements)

References 19 publications

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“…5) These rats develop spontaneous severe hypertension and obesity, and exhibit metabolic abnormalities (dyslipidemia, hyperinsulinemia and hyperglycemia), which are similar to those found in human metabolic syndrome. To date SHRSP-fatty have been used in studies that evaluated dysfunction of vasodilation mechanisms, cardiovascular remodeling, and atherogenic dyslipidemia in metabolic syndrome.…”

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confidence: 80%

Characterization of Cardiac Size and Function in SHRSP.Z-Leprfa/IzmDmcr Rats, a New Animal Model of Metabolic Syndrome

Tada

Kagota

Matsumoto

et al. 2010

Biological & Pharmaceutical Bulletin

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Lifestyle-related diseases-visceral obesity, hypertension, dyslipidemia and glucose intolerance-are known to appear in a cluster referred to as metabolic syndrome. As the number of disease components in metabolic syndrome increases in a patient, the structure and function of the heart becomes more compromised. 1) For example, metabolic syndrome increases the risk of atrial enlargement and fibrillation 2,3) and left ventricular hypertrophy and diastolic dysfunction. 1,4) These structural and functional abnormalities are considered to contribute to the increased cardiovascular morbidity and mortality associated with metabolic syndrome. However, the mechanisms underlying these abnormalities are not well understood.SHRSP.Z-Lepr fa /IzmDmcr rats (SHRSP-fatty) were established by crossing stroke-prone SHR (SHRSP/Izm) with Zucker obese rats to create a new animal model of metabolic syndrome.5) These rats develop spontaneous severe hypertension and obesity, and exhibit metabolic abnormalities (dyslipidemia, hyperinsulinemia and hyperglycemia), which are similar to those found in human metabolic syndrome. To date SHRSP-fatty have been used in studies that evaluated dysfunction of vasodilation mechanisms, cardiovascular remodeling, and atherogenic dyslipidemia in metabolic syndrome. [6][7][8] The aim of the present study was to characterize the cardiac structure and function in SHRSP-fatty. Increased cardiac stiffness induced by disturbed myocardial collagen turnover is suggested as one of the mechanisms of cardiac abnormalities in hypertension and diabetes.9,10) Therefore, as structural parameters, heart weight and a major myocardial collagen, collagen type I, as an index of fibrosis, were measured. Additionally, collagen type III, which contributes to tissue elasticity, was measured and the ratio of type I to type III was calculated as an index of myocardial stiffness. To assess cardiac function in SHRSP-fatty, heart rate, systolic blood pressure, cardiac output, blood flow and stroke volume were measured by tail-cuff and plethysmography, and compared to those in hypertensive lean SHRSP and normotensive lean WistarKyoto rats (WKY). Systolic and diastolic cardiac functions were also determined by echocardiography. The results may inform us whether this model would be a useful animal model to evaluate cardiac complications of metabolic syndrome. MATERIALS AND METHODS Experimental AnimalsMale SHRSP-fatty (nϭ18), SHRSP (nϭ18) and normotensive control WKY (nϭ18) were purchased at 16 weeks of age from Japan SLC, Inc. (Hamamatsu, Japan). The rats were established by the Disease Model Cooperative Research Association (Hamamatsu, Japan). Standard chow (CE-2; Clea Japan Inc., Tokyo, Japan) and water were available ad libitum during the experimental period. The study protocols were performed according to the Guideline for the Care and Use of Laboratory Animals approved by Mukogawa Women's University.Tail-Cuff Method and Plethysmography Systolic blood pressure and heart rate of conscious rats were meas- Cardiac structural and funct...

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confidence: 80%

Characterization of Cardiac Size and Function in SHRSP.Z-Leprfa/IzmDmcr Rats, a New Animal Model of Metabolic Syndrome

Tada

Kagota

Matsumoto

et al. 2010

Biological & Pharmaceutical Bulletin

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“…The SHRSP.ZF strain was established by crossing stroke-prone spontaneously hypertensive rats (SHRSP) and Zucker fatty rats (ZF). 23) Young SHRSP.ZF (10-13 weeks of age) exhibit similar characteristics of metabolic syndrome observed in humans including a slowly worsening progression with age. In Japan, people are diagnosed with metabolic syndrome based on waist circumference, as a surrogate estimated measure of visceral fat, and two or more criteria as follows: high blood pressure, high fasting blood glucose, high serum triglycerides, or low high-density lipoprotein-cholesterol.…”

Section: Changes In Par2-mediated Vasodilator Function At Early Stagementioning

confidence: 87%

Progression of Time-Dependent Changes to the Mechanisms of Vasodilation by Protease-Activated Receptor 2 in Metabolic Syndrome

Maruyama

McGuire

Kagota

2017

Biological & Pharmaceutical Bulletin

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Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteases released from tissues or by synthetic peptide ligands administered pharmacologically. Its wide expression in the cardiovascular system, particularly within the endothelium, vasodilation activity, and link to increased expression of inflammatory cytokines positions PAR2 as a potentially important regulator of vascular pathology under conditions of tissue inflammation, and injury; and thus, a pharmaceutical target for new therapeutics. Obesity is considered a chronic low-grade systemic inflammatory condition as inflammatory cytokines released from adipocytes are closely related to development of metabolic syndrome and related disorders. Our work over the past five-years has focused on the changes in vasomotor functions of PAR2 in metabolic syndrome, using an animal model known as the SHRSP.Z-Lepr fa /IzmDmcr rats (SHRSP.ZF). In young SHRSP.ZF that had already developed impaired responses to nitric oxide, we reported that PAR2-induced endothelium-dependent vasodilation is preserved. However, this PAR2 vasodilation decreased with increasing age and further chronic exposure to the conditions of metabolism disorder. These findings raise the possibility that PAR2 regulates tissue perfusion and can protect organs from injury, which is an increasing clinical concern at later stages of metabolic syndrome. Here we present our studies on the time-dependent changes in vasoreactivity to PAR2 in metabolic syndrome and the underlying mechanisms. Furthermore, we discuss the implications of these age-related changes in PAR2 for the cardiovascular system in metabolic syndrome.

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“…ZF rats were obtained from Tokyo Experimental Animals (Tokyo, Japan). SHRSP fatty rats were established by crossing SHRSP/Izumo with ZF rats as described previously ( 6 ). Systolic blood pressure (SBP) was measured by the tail-cuff method.…”

Section: Methodsmentioning

confidence: 99%

“…( 6 ) recently established a new rat model of metabolic syndrome, SHRSP.Z-Lepr fa /IzmDmcr, by crossing stroke-prone, spontaneously hypertensive rat (SHRSP) of the Izumo strain, a genetic model of severe hypertension, with Zucker fatty (ZF) rats. SHRSP fatty rat carry the leptin receptor OB-Rb gene mutation found in ZF rats.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Remodeling and Metabolic Abnormalities in SHRSP.Z-Leprfa/IzmDmcr Rats as a New Model of Metabolic Syndrome

Ueno¹,

Takagi²,

Fukuda³

et al. 2008

Hypertens Res

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Establishment of a new animal model of metabolic syndrome: SHRSP fatty (fa/fa) rats

Cited by 55 publications

References 19 publications

Characterization of Cardiac Size and Function in SHRSP.Z-Leprfa/IzmDmcr Rats, a New Animal Model of Metabolic Syndrome

Characterization of Cardiac Size and Function in SHRSP.Z-Leprfa/IzmDmcr Rats, a New Animal Model of Metabolic Syndrome

Progression of Time-Dependent Changes to the Mechanisms of Vasodilation by Protease-Activated Receptor 2 in Metabolic Syndrome

Cardiovascular Remodeling and Metabolic Abnormalities in SHRSP.Z-Leprfa/IzmDmcr Rats as a New Model of Metabolic Syndrome

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