Obese spontaneously hypertensive rats—A model for study of atherosclerosis

Koletsky, Simon

doi:10.1016/0014-4800(73)90040-3

Cited by 180 publications

(92 citation statements)

References 7 publications

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“…In this regard, the aim of this study was to investigate retina pathology in the SHR/N-cp model that combines type 2 diabetes and features of the metabolic syndrome, including obesity, hypertension and hyperlipidemia as well as insulin resistance. 13,15,31 In contrast to the more pronounced target organ damage previously reported in the cardiovascular system 12 and kidney, 17,18 histological analysis in this study revealed an intact integrity of the retina in obese animals. Specifically, azan and sirius red staining demonstrated no marked difference in the expression of matrix molecules.…”

Section: Discussioncontrasting

confidence: 77%

“…This rat strain was originally derived by mating a male Koletzky rat 12 that was heterozygous for the corpulent gene mutation (cp/+) to a female SHR rat of the Okamoto strain, with subsequent backcrosses to eliminate the non-cp genes of the Koletzky strain. Therefore, the SHR/N-cp is obese due to the cp mutation, which has been identified as a functional null mutation of the leptin receptor.…”

Section: Methods Animalsmentioning

confidence: 99%

“…We therefore set out to address this point in an experimental setting by investigating the retina in the obese and spontaneously hypertensive corpulent (SHR/N-cp) rat model. 12 This model combines obesity, type 2 diabetes, hypertension and hyperlipidemia 13 and exhibits a wide range of target organ damage; atherosclerosis, 12 hepatic steatosis, 14 pancreatic islet cell hyperplasia, 15 cardiomyopathy 16 and nephropathy 17,18 have been described in SHR/ N-cp. Furthermore, this model demonstrates an important feature of the metabolic syndrome, that is, insulin resistance, 19 which has also gained importance with regard to the pathogenesis of retinopathy, particularly retinal neovascularization.…”

Section: Introductionmentioning

confidence: 99%

“…20 Furthermore, SHR/N-cp resembles the slow progression of target organ damage in metabolic syndrome that can be observed during the lifespan of the animals over several months. 12 In this regard, SHR/N-cp contrasts sharply with the widely used STZ)-induced diabetes rat model. 21 Because STZ toxicity rapidly leads to destruction of the b-cells in the pancreas with acute insulin deficiency, loss of body weight and a pronounced reduction of lifespan, 22 this widely used model imitates type 1 diabetes but is quite different from the pathophysiology observed in type 2 diabetes and the metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

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Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

et al. 2010

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Retinopathy has been increasing in prevalence as a consequence of type 2 diabetes and a cluster of coexisting risk factors characterized as the metabolic syndrome. However, the combined effects of these conditions on the retina are poorly understood. Therefore, we focused on the spontaneously hypertensive corpulent rat (SHR/N-cp), a model with type 2 diabetes, obesity and features of the metabolic syndrome to characterize retinal changes at a structural and functional level. SHR/N-cp males at 4 and 8 months of age were used in this study. Metabolic parameters and blood pressure were measured by standard methods. Morphology was investigated by histological techniques supplemented by nicotinamide adenine dinucleotide phosphate-diaphorase staining of whole mounts and fluorescein angiography to analyze the retinal vasculature. The in vivo function of the retina was examined by electroretinography (ERG). Obese SHR/N-cp rats were hypertensive and showed significant increases in body weight, serum levels of glucose, triglycerides, total cholesterol and urinary glucose excretion compared with lean controls (Po0.01 for each). Histology indicated an overall intact integrity of the retina and aspects of microangiopathy in obese SHR/N-cp rats. ERG revealed intact processing of light signals but significantly decreased amplitudes of b-waves for all (Po0.01) and of a-waves for some examined light intensities (Po0.05). Oscillatory potentials were significantly protracted (Po0.01), whereas amplitudes were not reduced. Microangiopathy and electroretinographic deficits combine to produce an early non-proliferative retinopathy phenotype in the obese SHR/N-cp rats. Thus, this model represents a valuable experimental tool to obtain further insights into the mechanisms of retinopathy in the context of obesity, type 2 diabetes and metabolic syndrome.

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Section: Discussioncontrasting

confidence: 77%

Section: Methods Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

et al. 2010

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“…In 1973, Koletsky 18 described the spontaneous occurrence of obesity in a hypertensive rat (the Koletsky rat) that had descended from the mating of a spontaneously hypertensive rat (SHR) and a normotensive Sprague-Dawley rat. Breeding data from crosses of the Zucker rat and the Koletsky rat suggest that alleles at the same locus may be responsible for the obesity in these strains.…”

Section: *Statistically Significant Difference When Compared With Thementioning

confidence: 99%

The Zucker fatty rat as a genetic model of obesity and hypertension.

1989

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The association of hypertension with obesity has long been recognized; however, because of the lack of suitable animal models of obesity and hypertension, the pathogenesis of the high blood pressure associated with obesity remains poorly understood. We hypothesized that the Zucker fatty rat, a widely studied model of obesity and insulin resistance, might also be characterized by hypertension. Mean arterial pressure directly measured in the unanesthetized, unrestrained obese (fatty) Zucker rat was significantly greater than in two strains of nonobese control rats, the lean Zucker rat and the Lewis rat. The greater blood pressure in the obese rats was not dependent on hyperphagia or increased body weight per se since moderate caloric restriction, achieved by pair-feeding with lean rats, decreased weight gain but did not attenuate hypertension. Pair-fed obese rats retained less sodium than lean control rats, suggesting that greater blood pressure in the obese rats is not a consequence of increased renal retention of sodium. A unique feature of the Zucker strain is that the increased blood pressure appears to be specifically associated with the obese genotype. The findings suggest that the obese Zucker rat might provide a useful experimental model of obesity and hypertension. (Hypertension 1989;13:896-901) T he association of clinical hypertension (high blood pressure) with obesity is well recognized. In a recent survey in which body weight and blood pressure were measured in 1 million Americans, Stamler et al 1 found that hypertension was twice as prevalent in younger overweight subjects and 50% more prevalent in older obese individuals than in normal-weight control subjects. However, despite the well-established association between obesity and hypertension, the pathophysiological relation between obesity and hypertension remains poorly understood. Lack of information regarding the pathogenesis of the high blood pressure associated with obesity has been attributed, in part, to the lack of suitable animal models of obesity and hypertension.

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Nuclear cholesterol content and nucleoside triphosphatase activity are altered in the JCR:LA-cp corpulent rat

et al. 1996

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A nuclear pore complex-associated nucleoside triphosphatase (NTPase) activity is believed to provide energy for nuclear export of poly(A)+ mRNA. This study was initiated to determine if nuclear membrane lipid composition is altered during chronic hyperlipidemia, and what effect this has on NTPase activity. The JCR:LA-cp corpulent rat model is characterized by severe hypertriglyceridemia and moderate hypercholesterolemia, and thus represents an ideal animal model in which to study nuclear cholesterol and NTPase activity. NTPase activity was markedly increased in purified hepatic nuclei from corpulent female JCR:LA-cp rats in comparison to lean control rats as a function of assay time, [GTP], [ATP], and [Mg2+]. Nuclear membrane cholesterol and phospholipid content were significantly elevated in the corpulent animals. Nuclei of corpulent animals were less resistant to salt-induced lysis than nuclei of lean animals, suggesting a change in relative membrane integrity. Together, these results indicate that altered lipid metabolism in a genetic corpulent animal model can lead to changes in nuclear membrane lipid composition, which in turn may alter nuclear membrane NTPase activity and integrity.

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Obese spontaneously hypertensive rats—A model for study of atherosclerosis

Cited by 180 publications

References 7 publications

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

Microangiopathy and visual deficits characterize the retinopathy of a spontaneously hypertensive rat model with type 2 diabetes and metabolic syndrome

The Zucker fatty rat as a genetic model of obesity and hypertension.

Nuclear cholesterol content and nucleoside triphosphatase activity are altered in the JCR:LA-cp corpulent rat

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