선천성 고혈압 흰쥐와 정상혈압 흰쥐의 혈관 평활근 세포의 성장 특성

정재군,정현주,김인겸,김중영 慶北大學校 醫科大學 1997 慶北醫大誌 Vol.38 No.2

목적 : 선천성 고혈압 흰쥐(SHR)와 정상 혈압 흰쥐(WKY)의 혈관 평활근 세포를 배양하여, 그 성장 특성을 조사하였다. 대상 및 방법 : SHR 및 WKY를 pentobarbital(50㎎/㎏)로 마취하여 적출한 흉부대동맥으로부터 혈관평활근세포를 얻었으며 이 세포를 이차배양하여 일정한 시간간격으로 trypsin을 처리하여 세포를 떼어낸후 혈구계(hemocytometer)로 세포수를 헤아렸다. 결과 : SHR과 WKY에서 얻은 혈관평활근세포에서 형태학적 차이는 없었고, SHR이 WKY보다 밀생상태에 더 빨리 도달하며 밀생상태에 도달했을때 SHR이 WKY보다 세포밀도가 더 높게 나타났다. 결론: SHR이 WKY보다 증식속도와 증식밀도가 더 높게 나타나는 것으로 보아 SHR에 성장 억제 조절 기전의 장애가 있음을 시사한다. To study the generation and processes of hypertension, characteristics of vascular smooth muscle cell were observed in cultured aortic smooth mescle cell from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The degree of cell proliferation increased with escalating concentrations of fetal bovine serum(FBS) in cells of both SHR and WKY control rats. These results have shown that 10% FBS, which was the usual concentration in culture medium, was better concentration of medium in cell proliferation than 5% FBS, 10% calf serum, 10% horse serum, or 1% bovine serum albumin. There were no detectable differences in the morphology of cells obtained from SHR and WKY. Comparative studies have shown that cultured vascular smooth muscle cells from SHR proliferated to a higher cell number, grew to a greater density, and have greater specific growth rate than those of the WKY. These results provide possibility of a disturbances on inhibitory conrol to vascular smooth muscle cell growth in SHR.

해조성분 강화염이 본태성 고혈압쥐와 정상혈압쥐의 혈압, 혈청 중 미네랄 함량 및 생화학적 특성에 미치는 영향

김영명(Young-Myoung Kim),변지영(Jee-Young Byun),한찬규(Chan-Kyu Han),성기승(Ki-Seung Sung),남궁배(Bae NamGung) 한국식품과학회 2009 한국식품과학회지 Vol.41 No.2

본 연구는 해조성분 강화염을 본태성 고혈압쥐(SHR)와 정상혈압쥐(WKY)에게 6주간 급여하면서 혈압, 무기질 및 혈청 생화학치 등에 미치는 영향을 조사하고자 실시하였다. 실험처리는 laver salt, fucoidan+laver salt(high/low dose), refined salt(대조염)의 4처리로 하였고, 실험동물(SHR/WKY)은 완전임의배치법으로 각각 8마리, 6마리씩 배치하였다. 식염량은 1일 16 g을 기준으로 하여, +20% (고염식), ?20%(저염식)으로 설정하였으며, 식염은 음용수 형태로 6주 동안 급여하였다. 실험기간동안 수축기 혈압은 해조성분강화염 급여 후 3주까지는 상승하다가 이후 종료시까지 비슷한 수준을 유지(fucoidan+laver salt) 또는 감소하였으며(laver salt), 대조염군(정제염)은 지속적으로 증가하다가 마지막 주에 다소 감소하였다. 실험종료시 A군과 D군의 혈압차는 약 24mmHg로 나타났고, 기준혈압대비 종료시 혈압상승율은 D군의 17.6%에 비해 A군과 C군이 각각 8.2, 7.4%로 낮았다. WKY의 실험 6주의 D군과 C군의 혈압차는 8.5 mmHg로 나타났고, 기준혈압 대비 종료시 혈압감소율은 D군보다 C군에서 더 크게 나타나서 SHR과 비슷한 경향이었다. 혈청 미네랄 중 Na<SUP>+</SUP> 함량은 SHR과 WKY 모두 실험군간 차이가 없었고, K<SUP>+</SUP>은 SHR에서 fucoidan+laver salt 고염식군(B)이 높았으며, Mg<SUP>++</SUP>은 WKY에서 해조성분강화염군(A, B, C)이 유의하게 높았다(p<0.05). 혈당과 총 빌리루빈함량은 SHR에서 대조염군보다 해조성분강화염군에서 유의하게 낮았고, WKY 역시 혈당치는 해조성분강화염군이 유의하게 낮았다(p<0.05). 혈청 알부민은 SHR과 WKY 모두 laver salt군(A)이 유의하게 높았고(p<0.05), SGOT와 SGPT활성은 두 동물종 모두 해조성분강화염에서 낮았다. 혈청지질 중 TC농도는 대조염군보다 해조성분강화염군에서 통계적으로 낮았고, TG농도는 해조성분강화염 중 A군과 C군이 유의하게 낮았으며, HDL 및 LDL농도는 A군이 유의하게 높거나 낮았다(p<0.05). 이상의 결과에서 해조성분강화염중 laver salt는 대조염군과 같은 양의 식염을 섭취했음에도 미네랄 대사와 혈청 지질성분의 긍정적인 변화 등으로 인해 혈압상승을 적절하게 억제한 것으로 사료되었다. The effects of the salts fortified with seaweed functional components on blood pressure, serum minerals, and hematochemicals in spontaneously hypertensive rats (SHR/NCrj) and normotensive rats (WKY/NCrj) were investigated. SHR and WKY rats were assigned to four groups, with 8 and 6 rats in each group: laver salt (A), fucoidan+laver high salt (B), fucoidan + laver low salt (C) and refined salt as a control (D). The final blood pressure (BP) of SHR and WKY species in contrast with reference BP were low in groups A and C as compared with control group. In terms of serum mineral content, Na<SUP>+</SUP> levels were similar in SHR and WKY, but K<SUP>+</SUP> levels were higher in the group B in SHR. Serum triglyceride levels were lower in groups A and C, but the levels of HDL- and LDL- cholesterol were significantly higher and lower in group A than those of controls, respectively (p<0.05). These results demonstrated that the salts fortified with laver might suppress blood pressure in rats, and also may improve mineral and lipid metabolism.

Angiotensin 전환 효소 억제제가 Spontaneously Hypertensive Rat와 Wistar-Kyoto Rat의 적출대동맥에서 내피세포 의존적 이완에 미치는 영향

한형수,김중영 慶北大學校 醫科大學 1993 慶北醫大誌 Vol.34 No.2

내피세포의존적 혈관근 이완에 대한 enalapril과 captopril의 두 ACEI를 장기 처치가 미치는 영향을 확인하고자 SHR과 WKY의 적출대동맥을 이용하여 실험하였다. 이완제로는 acetylcholine, histamine 그리고 nitroprusside를 이용하였다. Acetylcholine에 의한 이완은 EDRF생성 억제제로 알려진 약제인 N^G-monomethyl-L-arginine(10^-4M)과 고농도의 potassium용액(25mM)에서 억제되었고 histamine에 의한 이완은 N^G-monomethyl-L-arginine(10^-4M)에 의해 억제되었다. SHR에 대한실험에서 ACEI 처처군을 대조군과 비교하였을때 histamine에 의한 이완반응이 ACEI 처치군에서 증가되었다. Histamine에 의한 이완은 N^G-monomethyl-L-arginine(10^-4M)을 처치한 경우에만 이완이 증가되었고 acetylcholine에 의한 이완에서는 N^G-monomethyl-L-arginine(10^-4M)과 고농도의 potassium용액(25mM)을 처치한 경우 모두에서 이완이 증가되었다. WKY에 대한 실험에서 ACEI 처치군을 대조군과 비교하였을 때 histamine에 이한 이완은 어느 경우에도 이완이 증가되지는 않았고 acetylcholine에 의한 이완은 어느 경우에도 이완이 증가되지는 않았고 acetylcholine에 의한 이완은 어느 경우에도 이완이 증가되지는 않았고 acetylcholine에 의한 이완이 증가되었는데 이러한 이완의 증가는 N^G-monomethyl-L-arginine(10^-4M)과 고농도의 Potassium용액(25mM)을 처치한 경우 모두에서 미약하지만 통계학적으로는 유의하게 나타났다. 내피세포 비의존성 이완제인 nitroprusside를 이용한 이완반응은 ACEI 처치에 의해 아무런 영향도 받지 않았다. 이상의 결과에서 ACEI는 SHR의 적출대동맥에서 EDRF와 EDHF의 작용을 모두 항진시키며 WKY에서도 미미하나마 유사한 양상을 보였다, 이러한 내피세포 의존적 이완의 항진은 ACEI의해 내피세포 기능이 정상화에 의한 것이라고 생각된다. Using the isolated aortic rings of the spontaneously hypertensive rats(SHR) and normotensive Wistar-Kyoto rats(WKY), we evaluated the effect of angiotensin converting enzyme inhibitros, captopril and enalapril, on the endothelium-dependent relaxation. Acetylcholine, histamine, and nitroprusside produced relaxation of isolated aortic ring from SHR and WKY. ACEI treatment enhanced histamine-induced relaxation in SHR but not in WKY. Acetylcholine-induced relaxation was inhibited by the presence of N^G-monomethyl-L-arginine(LNMMA) and high concentration of extracellular potassium and histamine-induced relaxation was inhibited by the presence of LNMMA only. In the studies with SHR the enhancing effect of ACEI on histamine-induced relaxation was shown in the presence of the high concentration of extracellular potassium but not in LNMMA and the effect of ACEI on acetylcholine-induced relaxation was shown in the presence of LNMMA and high concentration of extracellular potassium. In the studies with WKY the enhancing effect of ACEI on acetylcholine-induced relaxation was not prominent but statistically significant in the presence of the high concentration of extracellular potassium and in LNMMA but not significant in the case of histamine-induced relaxation. Relaxation by nitroprusside was not altered by ACEI treatmenmt in both SHR and WKY. These results demontstrated that ACEI altered both EDHF- and EDRF-dependent response promineantly in SHR and slightly in WKY. And we suggest that the augmentation of endothelium-dependent relaxation by ACEI may be largely due to the recovery of endothelial function.

EFFECTS OF ACUTE AND SUBACUTE ADMINISTRATION OF COCAINE ON DOPAMINERGIC SYSTEMS IN THE RAT STRIATUM

Lim, D.K.,Ho, I.K. The Korean Society of Toxicology Korea Environment 1990 Toxicological Research Vol.6 No.1

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.

Common prefrontal cortical gene expression profiles between adolescent SHR/NCrl and WKY/NCrl rats which showed inattention behavior

dela Peñ,a, Ike,Bang, Minji,Lee, Jinhee,de la Peñ,a, June Bryan,Kim, Bung-Nyun,Han, Doug Hyun,Noh, Minsoo,Shin, Chan Young,Cheong, Jae Hoon Elsevier 2015 Behavioural brain research Vol.291 No.-

<P><B>Abstract</B></P> <P>Factor analyses of attention-deficit/hyperactivity (ADHD) symptoms divide the behavioral symptoms of ADHD into two separate domains, one reflecting inattention and the other, a combination of hyperactivity and impulsivity. Identifying domain-specific genetic risk variants may aid in the discovery of specific biological risk factors for ADHD. In contrast with data available on genes involved in hyperactivity and impulsivity, there is limited information on the genetic influences of inattention. Transcriptional profiling analysis in animal models of disorders may provide an important tool to identify genetic involvement in behavioral phenotypes. To explore some of the potential genetic underpinnings of ADHD inattention, we examined common differentially expressed genes (DEGs) in the prefrontal cortex of SHR/NCrl, the most validated animal model of ADHD and WKY/NCrl, animal model of ADHD-inattentive type. In contrast with Wistar rats, strain representing the “normal” heterogeneous population, SHR/NCrl and WKY/NCrl showed inattention behavior in the Y-maze task. The common DEGs in the PFC of SHR/NCrl and WKY/NCrl vs. Wistar rats are those involved in transcription (e.g. <I>Creg1</I>, <I>Thrsp</I>, <I>Zeb2</I>), synaptic transmission (e.g. <I>Atp2b2</I>, <I>Syt12</I>, <I>Chrna5</I>), neurological system process (e.g. <I>Atg7</I>, <I>Cacnb4</I>, <I>Grin3a</I>), and immune response (e.g. <I>Atg7</I>, <I>Ip6k2</I>, <I>Mx2</I>). qRT-PCR analyses validated expression patterns of genes representing the major functional gene families among the DEGs (<I>Grin3a</I>, <I>Thrsp</I>, <I>Vof-16</I> and <I>Zeb2</I>). Although further studies are warranted, the present findings indicate novel genes associated with known functional pathways of relevance to ADHD which are assumed to play important roles in the etiology of ADHD-inattentive subtype.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We describe novel genes associated with inattention in SHR/NCrl and WKY/NCrl. </LI> <LI> These are genes involved in transcription, synapse transmission, immune system, etc. </LI> <LI> qRT-PCR validated expression patterns of <I>Grin3a, Zeb2, Vof-16</I> and <I>Thrsp</I>. </LI> <LI> Further studies are needed to determine their roles in ADHD inattentive subtype. </LI> </UL> </P>

Losartan이 Wistar-Kyoto Rat과 Sprague-Dawley Rat의 적출 대동맥 수축에 미치는 영향

김경재,한형수 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.4

목적 : Losartan을 적출대동맥에 처치하였을 때 phenylephrine과 KCI에 의한 수축반응의 감소가 일어난다고 하는데, 정상혈압 동물에서도 losartan이 수축력에 영향을 주는지 그리고 영향을 준다면 어떤 기전에 의해서 야기되는지를 검토 하고자 하였다. 대상 및 방법 : 생후 18주 이상된 정상혈압흰쥐 즉 SD와 WKY의 적출대동맥을 적출하여 90분간 losartan(10-5 M) 존재하에서 phenylephrin, KCI에 의한 수축반응과 histamine, nitroprusside에 의한 이완반응을 비교하였다. 결과 : Losartan을 90분동안 처치하면 phenylephrine과 KCI에 의한 수축 반응은 감소되었으나 phorbol ester에 의한 수축은 감소되지 않았다. 한편 losartan 존재하에서 nitric oxide synthase 억제제인 LNAME를 처치하면 수축력 감소가 나타나지 않았다. 그리고 histamine과 sodium nitroprusside에 의한 이완작용은 losartan 처치에 따른 영향을 받지 않았다. 결론 : 이상의 실험 결과에서 정상혈압에서도 losartan은 수축력 감소를 일으키며 이 작용은 protein kinase C 억제에 의한 것 같으며, losatan이 주로 basal release되는 nitric oxide에 영향을 주나, 외부자극에 의해 유리되는 nitric oxide와 cGMP에 의한 이완력에는 영향을 주지 않은 것으로 생각된다. It was aimed to evaluate the effect of losartan, angiotensin Ⅱ receptor blocker, on the contractile response of isolated aorta from normotensive rats, Sprague-Dawley and Wistar-Kyoto rats. Phenylephrine- and KCI-induced contractile responses were attenuated by losartan treatment(100 uM, for 90 min) but phorbol ester-induced contractile response was not attenuated. And in the presence of LNAMW(100 uM), attenuaton of phenylephrine-induced contractile response was not shown. Relaxing responses by histamine, endogenous nitric oxide releasing stimulator, and sodium nitroprusside, nitric oxide releaser, were not altered by losatan treatment. From these results it is suggested that losartan attenuates the contractile responses by inhibiting protein kinase C-mediated contraction and by enhancing basal release of nitric oxide.

WKY 랫드의 혈림프절 구조

박철범,성제경,이인세,이흥식,이준섭,윤여성,Park, Cheol-beom,Seong, Je-kyung,Lee, In-se,Lee, Heungshik S.,Lee, Joon-sup,Yoon, Yeo-sung 대한수의학회 2001 大韓獸醫學會誌 Vol.41 No.3

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.

Spontaneously Hypertensive Rat과 Wistar-Kyoto Rat 혈관 평활근 세포에서 Angiotensin Ⅱ에 의한 c-fos, PDGF-β, FGF-β, TGF-β 및 AT1A 수용체 유전자 발현 비교

한형수,정현주,양은경,김인겸 경북대학교 의학연구소 2000 경북대학교병원의학연구소논문집 Vol.4 No.1

Intrinsic differences between vascular smooth muscle cells(VSMC) in normotension and those in genetic hypertension may account for the exaggerated growth response often observed in the hypertensive vasculature. We investigated whether the differences in the growth properties between VSMC from 12 week old male spontaneously hypertensive rats(SHR) and those from normotensive Wistar-Kyoto rats(WKY) are related to the gene expression of c-fns, PDGF-β1, FGF-β, TGF-β1 and angiotensin Ⅱ receptor type 1A(ATIA). Growth stimulation to VSMC was done with angiotensin Ⅱ(1 μM) and mRNA levels for c-fos, PDGF-β, FGF-β, TGF-β1 and AT1A were measured by RT-PCR using each specific cDNA primers. In Angiotensin Ⅱ-untreated cases, VSMC from SHR exhibited higher mRNA leval for c-fos and PDGF-β than those from WKY . Following angiotensin Ⅱ treatment, increase in the level of mRNA for c-fos was more prominent in WKY than SHR. Angiotensin Ⅱ enhanced the gene expression of PDGF-β and FGF-β in both strains and made no change in AT1A and TGF-β1 gene expression. For FGF-β, there was no difference in the mRNA level between SHR and WKY following exposure to angiotensin Ⅱ. We concluded that difference in the growth properties of VSMC between SHR and WKY may be related to gene expression of c-fos and PDGF-β.

Glycine이 적출 정상 및 자발성 고혈압 백서 대동맥 평활근의 수축성에 미치는 효과

강석한,신태순,고상돈,김기순 한양대학교 의과대학 1992 한양의대 학술지 Vol.12 No.1

Glycine has been known to possess significant cardiovascular effects. Electrophysiological effects of glycine were demonstrated in the rabbit sinus node cells. Recently it was also reported that glycine induced endothelium-dependent contractions in the isolated rabbit aorta. On the other hand, it has been generally agreed that the vascular reactivity was also altered in spontaneously hypertensive rats(SHR). The present study was performed to investigate effects of glycine on the vascular smooth muscle in the 16 week old Wistar-Kyoto rats(WKY) and in the age-matched SHR. The systolic pressures of WKY and SHR were 123.9±9.4mmHg and 198.5±8.5mmHg, respectively. Glycine(10-100mM) produced endothelium-dependent contractions in the isolated aortic rings of both WKY and SHR. At concentration of 50mM glycine increased vascular tension respectively by 60.2±6.9%(percentage to contraction induced by 1×10 M) and 89.4±2.9% in WKY and SHR. After denudation the vascular responmses to 50mM glycine solution were respectively 25.4±1.8 and 34.2±1.4% in WKY and SHR. Also hyperosmolarity provoked vascular contractions. Following superfusion with 370mOsm Krebsmannitol solution which ws equimolar with 50mM glycine solution, vascular tension increased by 24.5±4.7% in both animal groups. The results indicate that glycine may produce endothelium-dependent contractions in the isolated aorta of SHR, and that vascular responses to glycine are more sensitive in SHR.

A Simple Behavioral Paradigm to Measure Impulsive Behavior in an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD) of the Spontaneously Hypertensive Rats

( Pitna Kim ),( In Ha Choi ),( Ike Campomayor Dela Pena ),( Hee Jin Kim ),( Kyung Ja Kwon ),( Jin Hee Park ),( Seol Heui Han ),( Jong Hoon Ryu ),( Jae Hoon Cheong ),( Chan Young Shin ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.1

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.