• Biomolecules & Therapeutics
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• v.10 no.3
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• pp.193-199
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• 2002

The arylamine N-acetyltransferases (NATs) are a family of enzymes that N-acetylate mylhydrazines and arylamines through transfer of an acetyl group from acetyl coenzyme A. This activity was found to vary among individuals as a Mendalian trait and the basis of the genetic differences in human NAT activity is one of the best of the genetic studied examples of pharmacogenetic variation. The classical N-acetylation polymorphism is regulated at the NAT2 locus, which segregates individuals into rapid, intermediate, and slow acetylator phenotypes. In this study, the relationship between NAT2 activity phenotype using HPLC:UV assay for the determination of dapsone and monoacetyldapsone in plasma and NAT2 genotype by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was investigated in the F2 hybrid (Fischer 344 vs Wistar-Kyoto) rats. Three Common mutant alleles at the NAT2 gene locus have been identified in the F2 generation progeny of Fischer 344 rats as raid acetylator and Wistar-Kyoto rats as slow acetylator segregated into three modes (low, intermediates, and high) with simple Mendelian inheritance. The metabolic activity of NAT2 of the intermediate and rapid acetylators is significant1y greater than slow acetylator, but the metabolic activity of rapid acetylator is not significantly different from Intermediate type. Therefore, we could observe that complete trimodal NAT2 genotypic alleles and incomplete trimodal NAT2 metabolic phenotypic distribution in tile F2 hybrid rats. These observations suggest that the relationships between NAT2 genotype and metabolic phenotype exists and F2 hybrid (Fischer 344: Wistar-Kyoto) animal models about NAT2 polymorphism might be applied in the toxicity and pharmacogenetic studies of arylamine drugs and carcinogens.

• YAKHAK HOEJI
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• v.59 no.4
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• pp.184-189
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• 2015

We compared impulsive behaviors in Wistar rats and in Wistar-Kyoto rats. There was no significant difference in locomotor activity between them. However, Wistar rats showed high activity in 5-choice serial reaction time track. When Wistar rats were treated with atomoxetin (3 mg/kg), methylphenidate (2 mg/kg) or amphetamine (2 mg/kg), they showed less impulsive behavior. Serotonin contents in prefrontal cortex and brain stem also increased. In conclusion, we suggest that Wistar rats could be used as animal model for impulsive behavior analysis. In addition, serotonin might be related with this impulsivity.

• Korean Journal of Pharmacognosy
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• v.30 no.2
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• pp.226-230
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• 1999

We have isolated a sesquiterpene lactone, cumambrin A from the dried flowers of Chrysanthemum boreale Makino and reported its chemical structure. The aim of the present study was to investigate whether the exogenous administration of cumambrin A has a pharmacological effect on normalization of blood pressure in the spontaneously hypertensive rats (SHR). In vitro studies: Relaxative response induced by cumainbrin A was increased with dose-dependent manner and showed maximizing response at a concentration of $5{\times}10^{-4}M$. Further, this relaxative response was significantly increased at a condition of endothelium present than that of endothelium denuded. In vivo studies: The normalizing effect of cumambrin A on blood pressure was also increased with time-dependent manner and then gradually recovered to normal condition at approximately 4 hrs after cumambrin A treatment.

• Archives of Pharmacal Research
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• v.11 no.4
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• pp.301-307
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• 1988

Relationship between the maintenance of hypertension and central serotonergic nervous system activity in opontaneously hypertensive rats (SHR) was studied. Serotonin turnover-rates were measured in 5 brain areas as an index of serotonergic neuronal activity and compared at the ages of 14 weeks in two types of animals; (1) spontaneously hypertensive rats (SHR) (2) normotensive wistar kyoto rats (WKY). In 14-week old SHR, central serotonin turnover rate was significantly lower in telencephalon, hypothalamus/thalamus and midbrain than normotensive rat, but significantly higher in cerebellum. There were no significant differences between serotonin turnover rate in pons/medulla of SHR and that of normotensive rat. THese data suggest that the abnormally lower turnover rates of serotonin in telencephalon, hypothalamus/thalamus and midbrain may be one of the underlying neuronal factors for manifestation of hypertension in SHR.

• Journal of Life Science
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• v.22 no.5
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• pp.665-670
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• 2012

This study investigated the effect of endurance exercises on blood pressure, angiogenesis, and the vascular endothelial growth factor (VEGF) expression in the skeletal muscle of spontaneously hypertensive rats (SHR). Five week old SHRs and Wistar-Kyoto rats (WKY) were randomly divided into 3 groups: Wistar-Kyoto rats (WKY, n=9), SHR control (SHR-C, n=9), and SHR endurance exercise training (SHR-E, n=9). Endurance exercise training was performed on a treadmill (12-20 m/min, 0% grade, 60 min/day, 5 days/week, 16 weeks). Systolic blood pressure was monitored with the tail-cuff method. The expression of VEGF protein and capillary density were identified using western blotting and H&E staining in the soleus muscle, respectively. Systolic blood pressure was reduced by endurance exercise in SHR ($p$ <0.05). The capillary density of skeletal muscles in SHR-C was lower than in WKY ($p$ <0.05), but it was recovered by endurance exercise training (SHR-E) compared to SHR-C ($p$ <0.05), and VEGF protein was also increased by endurance exercise training compared to SHR-C ($p$ <0.05). These data suggest that the enhancement of capillary density via an increase of VEGF expression in skeletal muscles by endurance exercise training could be an important factor to inhibit blood pressure elevation in SHR.

• Toxicological Research
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• v.31 no.2
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• pp.173-180
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• 2015

Extract from Gryllus bimaculatus crickets inhibits oxidation at the DNA level, with reduced production of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Microarray analyses were performed with a rat 28K cDNA clone set array to identify the gene expression profiles of aged (10 months old) Wistar Kyoto rats treated for one month with 100 mg/kg G. bimaculatus ethanol extract to assess the effects. The extract produced a meaningful anti-edema effect, evident by the inhibition of creatinine phosphokinase activity. The weights of abdominal and ovarian adipose tissues were reduced and the proportion of unsaturated fatty acids in adipose tissues was increased in an extract dose-dependent manner. Compared with untreated control rats, rats treated with the extract displayed the upregulation of 1053 genes including Fas (tumor necrosis factor receptor superfamily, member 6), Amigo3 (adhesion molecule with an immunoglobulin-like domain), Reticulon 4, 3-hydroxy-3-methylglutaryl-coenzyme (Hmgcr; a reductase), related anti-fatigue (enzyme metabolism), and Rtn antioxidant, and the downregulation of 73 genes including Ugt2b (UDP glycosyltransferase 2 family), Early growth response 1, and Glycoprotein m6a. Data suggest that G. bimaculatus extract may have value in lessening the effects of aging, resulting in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.300-300
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• 1994

$Na^{+}$,$K^{+}$-ATPase activity, $Na^{+}$-dependent phosphorylalion, and [$^3$〕ouabain binding in sarcolemma prepared from 4 week old spontaneously hypertensive rat(SHR) ventricles were compared to the same parameters in sarcolemma from age matched normotensive Wistar-Kyoto(WKY) rat ventricles to examine whether the reduced myocardial $Na^{+}$-pump activity in SHR is an inherited enzymatic defect or a second phenomenon due to sustained hypertension. The total body weights, ventricular weights, and blood pressures were the same for SHR and WKY. No significant differences in sarcolemmal protein content and protein recovery were noted between the two pups. Sarcolemma isolated from SHR ventricles showed sigificantly less $Na^{+}$,$K^{+}$-ATPase activity and number of phosphorylation sites when compared to snrcolemma 1mm the WKY ventricles. Equilibrium binding of [$^3H$〕ouabain and the turnovcr number of myocardial $Na^{+}$,$K^{+}$-ATPast however, wee the same for both groups. These results. indicate that the low affinity(${\alpha}$, or ${\alpha}_1$) isoform for ouabain is reduced in SHR compared to WKY but that the high affinity(${\alpha}$+, or ${\alpha}_2$) isoform is the same in ventricles of SHR and WKY. The reduced amount of at isoform of the $Na^{+}$,$K^{+}$-ATPasc in prehypertensive SHR ventricles may play some pole in the development of hypertension.

• Journal of Life Science
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• v.15 no.5 s.72
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• pp.703-706
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• 2005

The purpose of this study is to investigate the combined effect of L-arginine supplementation and regular physical exercise on HR, BP, eNOS and Macrophage activation using SHR. To examine the differences among HR, BP, eNOS, and Macrophage activity levels, normotensive Wistar-Kyoto rats were used as a control. Thirty two male rats (six weeks old) were divided into four groups; eight WKY control (WKYC), eight SHR control (SHRC), eight SHR supplemented with L-arginine (SHRA), and eight SHR trained and supplemented with L-arginine (SHRTA). Obtained results were as follows : In the heart and blood pressure, there was significant differences anong the four group (p<.05) compare to SHRC. In the eNOS levels, there was significant differences among the four groups (p<.05) compare to SHRC. In the macrophage activity, there was significant differences among the four groups (p<.05) compare to SHRC. In conclusion, For the SHRC group, the level of eNOS is higher than that of WKYC, and we can expect tissue damage caused by toxic free radical. However, this can be stabilized by the L-arginine supplementation and regular physical training. we can also conclude regular aerobic training decrease cardiovascular stress caused by stabled macrophage activity. Therefore, we can trace it is the effect of training in SHR.

• Korean Journal of Veterinary Research
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• v.37 no.2
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• pp.405-408
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• 1997

랫트는 간질에 높은 감수성을 나타내기 때문에 간질의 연구에 실험실 모델로 많이 이용된다. 그러나 간질의 피낭유충을 랫트에 감염시킨 다음 랫트의 분변에서 충란을 검출해보면 충란의 검출률은 100%에 훨씬 못미쳐서 실험의 설계에 어려움을 겪는 경우가 흔하다. 이 연구에서는 우리나라에서 많이 사육되고 있는 4가지 스트레인(Sprague-Dawley, Fisher 344, the spontaneously hypertensive rats 그리고 Wistar-Kyoto)의 암 수 랫트에 간질의 피낭유충을 경구적으로 접종하고 분변검사와 부검을 실시하여 감염여부를 확인하였다. 충체회수율은 랫트의 성과 스트레인 간에 유의성 있는 차이를 보였는데 Sprague-Dawley계의 랫트가 가장 높은 충체회수율을 보였으며 평균 충체회수율은 암컷보다 수컷에서 높았다. 이 연구의 결과는 간질에 관한 연구 특히 간질구충제의 효능을 검정하는 시험에 유용한 지침이 될 것으로 사료된다.

• Korean Journal of Veterinary Research
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• v.37 no.4
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• pp.719-726
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• 1997

Dorsal root ganglion(DRG) cells are primary sensory neurons which contain some biologically active neuropeptides which play a role as neurotransmitters or neuromodulators. This study was performed to observe normal distribution of calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactive cells and colocalization of CGRP and SP in a single DRG cell of the lumbar DRGs($L_1{\sim}L_6$) in the Wistar Kyoto(WKY) rat by immunohistochemistry. About 55.8% of DRG cells contained CGRP-immunoreactivity, while about 12.7% of DRG cells showed SP-immunoreactivity. There was no significant difference in percentage of each neuropeptied-immunoreactive cells between each neuropeptide-immunoreactive cells between each levels of DRGs ($L_1{\sim}L_6$) (p>0.01). In size distribution, CGRP-immunoreactive cells were identified below $1,500{\mu}m^2$; SP-immunoreactive cells below $600{\mu}m^2$. In serial sections, about 86.7% of the SP immunoreactive cells contained CGRP immunoreactivity.