• Proceedings of the Korean Society of Applied Pharmacology
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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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.

• Archives of Pharmacal Research
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• 제16권4호
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• pp.305-311
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• 1993

$Na^+,K^+$-ATPase activity, $Na^+$-dependent phosphorylation, and $[^3H]$ 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 nomotensive Wister-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 groups. Sarcolemma isolated from SHR ventricles showed significantly less $Na^+,K^+$-ATPase activity ande number of phosphorylation sites when compared to sarcolemma from the WKY ventricles. Equilibrium binding of $[^3H]$ouabain and the tumover number of myocardial $Na^+,K^+$-ATPase, however, were the same for both groups. These reults indicate that the low affinity $(\alpha,\;or\;\alpha^1)\;\alpha$ isoform is the same in ventricles of SHR and WKY. The reduced amount of isoform of the $Na^+,K^+$-ATPase inprehypetensive SHR ventricles may play some role in the development of hypertension.

• Toxicological Research
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• 제6권1호
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• pp.75-88
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• 1990

The characteristics of dopamine uptake, D-1 and D-2 receptors after acute and subacute cocaine administration were determind in striatum from WKY and SHR. Cocaine was administered either acutely (40 mg/kg, s.c.) or twice daily (20 mg/kg, s.c.) for 3 and 7 days in 9-wk old WKY and SHR. Rats were sacrificed 30 min, 2 or 24 h after the single injection and 18 h after the last administration to the subacutely treated group. The changes in dopamine uptake, dopamine uptake sites, D-1 and D-2 receptors were determined using $(^3H)$dopamine, $(^3H)$-GBR-12935, $(^3H)$SCH-23390 and $(^3H)$sulpiride, respectively. In acutely treated rats, significant increases in $V_{max}$of dopamine uptake were observed 30 min after the cocanine injection in both strains without changes in $K_m$ values. The in vitro $IC_{50}$for cocaine was significantly decreased 30 min in WKY and 2 h in SHR. However, that for in vitro GBR-12909 was significantly increased 30 min and 2 h in both strains. Also densities of $(^3H)$-GBR-12935 binding sites were significantly increased 30 min and 2 h without changes in their $K_d$. Significant increases in D-2 receptor density were observed 30 min, 2 or 24 h after acute injection in both strains without changes in their affinities. The density of D-1 receptor was significantly decreased 30 min after the injection in WKY, but not in SHR. In subacutely treated rats, a significant increase in $K_m$ of dopamine uptake was observed in 7-day treated SHR. The in vitro $IC_{50}$fot GBR-12909 was significantly increased in 3-day treated WKY. The density of D-1 receptors was significantly increased in 3- and 7-day treated WKY, but not in SHR. The affinity of both binding sites remained unchanged. The results suggest that cocanine administration alters dopamine uptake, characteristics of dopamine uptake sites and dopamine receptor binding characteristics in rat brain. Furthermore, D-1 and D-2 dopamine receptors appear to be differently regulated.

• The Korean Journal of Physiology and Pharmacology
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• 제1권4호
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• pp.385-392
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• 1997

The phospholipase C (PLC)-mediated intracellular signal transduction pathway is considered to be involved in the regulation of blood pressure. However, little information is available concerning the distributional and functional significance of PLC in the genetic hypertensive rats. As the first step of knowing the role of PLC on hypertension, we investigated the distribution of 6 PLC isozymes $(PLC-{\beta}1,\;-{\beta}3,\;-{\beta}4,\;-{\gamma}1,\;-{\gamma}2\;and\;-{\delta}1)$ in the heart and brain, which are concerned with hypertension, in the normotensive Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR) using the western blotting and immunocytochemistry. The immunoreactivities of PLC isozymes in brain were detected, but there were no distributional and quantitative differences between the WKY and SHR. In the heart, but the immunoreactivities to $PLC-{\beta}1$ and $-{\gamma}2$ in the SHR were higher than those in WKY. In immunocytochemistry to confirm these western blotting data, $PLC-{\beta}1$ and $-{\gamma}2$ were localized in cardiac myocytes and the intensities of immunoreactivity in SHR were stronger than that in WKY. These results suggest that $PLC-{\beta}1$ and $-{\gamma}2$ would have possibility to concern with the establishment of spontaneous hypertension.

• Korean Journal of Veterinary Research
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• 제47권1호
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• pp.7-17
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• 2007

The left main descending artery (LMDA) of left coronary artery (LCA) in rats runs around the left side of conus arteriosus after arising from the aortic sinus and descends to the apex of heart with branching several branches into the wall of left ventricle (LV). The ligation site of LMDA for myocardial infarction (MI) is the 2~4 mm from LCA origin, between the pulmonary trunk and left auricle. The characteristics that rat heart has no interventricular groove on the surface and its coronary arteries run intramyocardially with branching several branches give the difficulty in surgery for MI which resulted in expected size. This study was aimed to elucidate the branching patterns of the left coronary artery for analysis of MI size and for giving the basic data to producing small MI intentionally in 2 male species that are widely used, Sprague-Dowley (SD) and Wistar-Kyoto (WKY), in the world. Red latex casting was followed by the microdissection in 27 and 28 hearts of SD and WKY male rats, respectively. The branching patterns of LMDA were classified into 3 major types and others based on the left ventricular branches (L). The Type I, Type II, Type III and others are shown in 55.6%, 22.2%, 14.8%, and 7.4% in SD, 60.7%, 10.7%, 7.1%, and 21.5% in WKY, respectively. The branching number of the first left ventricular branch (L1) that are distribute the upper one third of LV was 1.2~1.5, and its branching sites were ranging 0.9~2.1 ᒠfrom LCA origin. L2, the second left ventricular branch distributing middle one third of LV, was the number of 1.2~1.4 and branching out ranging 5.1~5.7 mm. L3, the third left ventricular branch of LMDA distributing lower one third of LV, was the number of 1~1.5 and branching out ranging 7.0~9.3 mm from LCA origin. The common branch of L1 and L2 was branched from LMDA with the number of 1.1, and its site was located in the distance of mean of 1.5 mm and 2.8 mm in SD and WKY, respectively. The common branch of L2 and L3 was branched from LMDA with the number of 1, and its site was located in the distance of mean of 7.2 mm and 2.9 mm in SD and WKY, respectively. The right ventricular branches (R) of LMDA were short and branched in irregularly compared with L. The number of 1~4 of R were branched from LMDA. With regarding to the distribution area of L and the ligation site for MI, moderate MI (25~35% of LV) might be resulted in 70.4% and 60.7% in SD and WKY rats. Small MI might be produced intentionally if the ligation would be located at the 4~6 mm from LCA origin in the left side of LMDA. These data wold be helpful to expect the size of MI and to reproduce of small MI, intentionally, in rat hearts.

• Korean Journal of Veterinary Research
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• 제37권4호
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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.

• Korean Journal of Veterinary Research
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• 제41권3호
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• pp.287-292
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• 2001

It has been known that the hemolymph node is one of the lymphoid organs found normally in ruminants and some rodents, and this organ shares morphological and functional characteristics of lymph node and spleen. To clanify the rigorous definition of morphological structures and functions of the hemolymph node in Wistar Kyoto(WKY)rats, we examined these organs of WKY rats gross anatomically and light microscopically. The hemolymph nodes were normally found in the abdominal cavity and in the neck of WKY rats. This organ was surrounded by a thin connective tissue capsule and there was a hilus. The parenchyma comprised a cortex of lymphatic nodules and diffuse lymphatic tissues, and a medulla of diffuse lymphatic tissues arranged in cords. Afferent and efferent lymph vessels were observed but there was no extensive subcapsular and medullary sinuses. These sinuses were filled with erythrocytes. The stroma of hemolymph nodes was composed of reticular cells and fibers, and many lymphocytes, granulocytes, erythrocytes, plasma cells, macrophages and megakaryocytes were supported by the reticular network. The above findings suggest that the hemolymph nodes of WKY rats may take part in blood formation, blood filtration and immune reaction.

• Biomolecules & Therapeutics
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• 제20권1호
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• pp.125-131
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• 2012

Impulsiveness is an important component of many psychiatric disorders including Attention-deficit/hyperactivity disorder (ADHD). Although the neurobiological basis of ADHD is unresolved, behavioral tests in animal models have become indispensable tools for improving our understanding of this disorder. In the punishment/extinction paradigm, impulsivity is shown by subjects that persevere with responding despite punishment or unrewarded responses. Exploiting this principle, we developed a new behavioral test that would evaluate impulsivity in the most validated animal model of ADHD of the Spontaneously Hypertensive rat (SHR) as compared with the normotensive "control" strain, the Wistar Kyoto rat (WKY). In this paradigm we call the Electro-Foot Shock aversive water Drinking test (EFSDT), water-deprived rats should pass over an electrified quadrant of the EFSDT apparatus to drink water. We reasoned that impulsive animals show increased frequency to drink water even with the presentation of an aversive consequence (electro-shock). Through this assay, we showed that the SHR was more impulsive than the WKY as it demonstrated more "drinking attempts" and drinking frequency. Methylphenidate, the most widely used ADHD medication, significantly reduced drinking frequency of both SHR and WKY in the EFSDT. Thus, the present assay may be considered as another behavioral tool to measure impulsivity in animal disease models, especially in the context of ADHD.

• The Korean Journal of Physiology
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• 제30권2호
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• pp.269-278
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• 1996

The mechanism of impaired endothelium-dependent relaxation in the aorta of one-kidney, one clip Goldblatt hypertensive (1K,1C-GBH) rats was investigated. 8 week-old Wistar-Kyoto (WKY) rats were made hypertensive by left renal artery stenosis with contralateral nephrectomy. Endothelium-dependent relaxation was significantly reduced in 1K,1C-GBH rats as compared with WKY rats. However, the relaxation by sodium nitroprusside in 1K,1C-GBH rats was not reduced as compared with WKY rats. The impairment of endothelium-dependent relaxation in 1K,1C-GBH rats was partially restored by the pretreatment of indomethacin or SQ29548. When the nitric oxide production was inhibited by L-nitroarginine methyl ester, acetylcholine (ACh) induced a endothelium-dependent contraction that was greater in 1K,1C-GBH rats than in WKY rats. Endothelium-dependent contraction by ACh was completely abolished by indomethacin or SQ29548. However, imidazole, tranylcypromine and superoxide dismutase did not affect the endothelium-dependent contraction in 1K,1C-GBH rats. These results suggest that impaired endothelium-dependent relaxation in the 1K,1C-GBH rats might be due to the simultaneous release of EDCF, and that prostaglandin B2 may be involved as a mediator of endothelium-dependent contraction.

• The Korean Journal of Pharmacology
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• 제28권1호
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• pp.1-9
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• 1992

Catecholamines, serotonin and their metabolites were measured in the posterior hypothalamus of urethane-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) using brain microdialysis which is a recently developed experimental method to measure the release of neurotransmitters and their metabolites at the localized brain area in vivo. Microdialysis probe was implanted stereotaxically to the rat posterior hypothalamus and perfused by Ringer's solution. Monoamines and their metabolites were quantified by reverse phase high performance liquid chromatography with electrochemical detection. In vitro recovery test of microdialysis showed that there exist inverse relationship between the perfusion flow rate and the relative recovery of neurochemical compounds. The estimated extracellular concentration of dopamine was about 32 nM, of norepinephrine 50 nM, of epinephrine 50 nM, of serotonin 73 nM, of 3, 4-dihydroxyphenylacetic acid (DOPAC) 281 nM, of homovanillic acid (HVA) 181 nM, and of 5-hydroxyindoleacetic acid (5HIAA) 3767 nM in the hypothalamic perfusate of the normotensive rat. There was no difference in the basal level of monoamines between the SHR and the WKY. In contrast, the level of DOPAC, HVA and 5HIAA in SHR was higher than that in the WKY, This study demonstrated that the microdialysis technique should be an applicable tool for in vivo measurement of central neurochemical substances.