• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.29-34
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• 1999

The hyperactivity of cholinergic system in the RVLM of spontaneously hypertensive rats (SHR) may contribute to the sustained elevation of blood pressure. However, the hyperactivity mechanisms of cholinergic system are controversial. Thus, to clarify the mechanisms of cholinergic hyperactivity in RVLM of the SHR, we studied the activities of enzymes that participate in the biosynthesis and degradation of acetylcholine (ACh) and the density of muscarinic receptors in RVLM of the 14- to 18-week-old SHR and age-marched Wistar Kyoto rats (WKY). Choline acetyltransferase activity was far greater in RVLM of SHR than that of WKY. $[^3H]ACh$ release from RVLM was also greater in SHR than in WKY. Acetylcholinesterase activity and $[^3H]NMS$ binding of RVLM slice of SHR were not significantly different from that of WKY. These results suggest that the enhanced cholinergic mechanisms in the RVLM of SHR is due to the enhanced presynaptic cholinergic tone rather than the altered postsynaptic mechanisms.

• Biomolecules & Therapeutics
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• 제5권4호
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• pp.336-343
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• 1997

The purpose of the present study was to address whether the in vivo noradrenergic neural activities in the locus coeruleus are related to the development of hypertension. Two groups of the animals were prepared, 1) young SHR and 2) age-matched normotensive control, WKY. At the age of 6 weeks, blood pressure and the releases of NE and DOPEG from the locus coeruleus in young SHR and WKY were measured by in vivo microdialysis at two different conditions; 1) normal and 2) elevated state of blood pressure by systemically injected phenylephrine. Basal releases of NE and OOPEG from the locus coeruleus were $0.415 \pm$0.089 pg/20 min and $1.311 \pm0.293$ pg/20 min in SHR and $0.204\pm0.078$ pg/20 min and $1.472\pm 0.365$ pg/20 min in WKY The basal release of NE of SHR was significantly greater than that of WKY. Phenylephrine treatment caused elevation of blood pressure in both SHR and WKY in dose-dependent manner. Following phenylephrine injection, the releases of NE and DOPEG from the locus coeruleus of SHR were significantly decreased, whereas there was no significant changes of NE in WKY. The results from the present study suggests that the noradrenergic nervous system in the locus coeruleus may contribute as one of the triggering factors for the expression of hypertension in young SHR.

• The Korean Journal of Physiology
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• 제30권1호
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• pp.11-20
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• 1996

To investigate the properties of cromakalim-opened $K^{+}\;channels$ in aorta of spontaneously hypertensive rats (SHR), the effect of cromakalim on tension was compared in endothelium-rubbed aortic rings from SHR and normotensive Wistar-Kyoto rats (WKY). 1. Cromakalim relaxed the aortic ring contracted by $10^{-7}$ M norepinephrine (NE) dose-dependently, and this relaxant response to cromakalim was blocked by $10^{-5}$ M glybenclamide. 2. Cromakalim also relaxed the contraction induced by high $K^{+}$-solution or 10 mM tetraethylammonium dose-dependently. However, the relaxant response to cromakalim was decreased by raising the $K^{+}$ concentration. 3. SHR aorta exhibited myogenic tone in resting state which was inhibited by cromakalim, verapamil or $Ca^{2+}-free\;PSS.$ Whereas, WKY aorta did not exhibit any myogenic tone in resting state. 4. When aortic rings from both strains were contracted by $20\;mM\;K^{+}\;or\;NE$, relaxant responses to low concentration of cromakalim $(below\;10^{-7}\;M)$ were not different between WKY and SHR, but maximum relaxant response to cromakalim $(above\;3{\times}10^{-7} \;M)$ was greater in SHR than in WKY. 5. When the relaxant response to cromakalim was expressed as percent of maximum relaxation induced by $Ca^{2+}-free\;PSS$, relaxant response to cromakalim in 20 mM $K^{+}-induced$ contraction was not different between WKY and SHR. From the above result, it is suggested that relaxant responses to cromakalim are greater in SHR than WKY, and this may be due to the myogenic tone of aortic rings from SHR.

• 한국식품과학회지
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• 제41권2호
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• pp.196-202
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• 2009

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 16g을 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 $Na^+$ 함량은 SHR과 WKY모두 실험군간 차이가 없었고, $K^+$은 SHR에서 fucoidan+laver salt 고염식군(B)이 높았으며, $Mg^{++}$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 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 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.

• 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.

• 생명과학회지
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• 제22권5호
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• pp.665-670
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• 2012

이 연구는 자연발생고혈압쥐(SHR)의 혈압, 골격근에서의 혈관생성 및 혈관내피세포성장인자 발현(VEGF)에 미치는 지구성운동의 효과를 조사하였다. 5주령 SHR와 WKY는 무작위로 정상혈압군(WKY, Wistar-Kyoto rat, n=9), 고혈압통제군(SHR-C, SHR Control, n=9) 및 고혈압운동군(SHR-E, SHR Exercise, n=9)으로 각각 분류하였고, 지구성운동은 트레드밀을 이용하였다(12-20 m/min, 0% grade, 60 min/day, 5 days/wk, 16 wk). 수축기혈압은 지구성운동에 의해 효과적으로 감소되었다(SHR-E vs. SHR-C, $p$ <0.05). 골격근의 모세혈관밀도와 VEGF 단백발현은 고혈압통제군(SHR-C)이 정상혈압군(WKY)보다 모두 감소되었으나, 지구성운동(SHR-E)이 고혈압통제군(SHR-C)에 비해 모두 증가되었다. 이러한 결과들은 지구력운동 트레이닝이 SHR 골격근의 VEGF 단백발현의 증가를 통해 모세혈관밀도를 향상시키고, 이러한 모세혈관밀도의 향상이 SHR의 혈압상승을 억제할 수 있다는 것을 의미한다.

• 대한수의학회지
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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.

• The Korean Journal of Physiology
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• 제28권1호
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• pp.27-35
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• 1994

We investigated the alterations in basal tone of aortic strips by changing the Ca concentration, basal $^{45}Ca$ uptake and $^3H-nitrendipine$ binding of the single cells of aortic smooth muscles in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. While the basal tone of the aortic strips in WKY rats was not affected by alteration of Ca concentration, that in SHR was decreased by the removal of Ca from the bath solution and was recovered by the restoration of Ca to normal levels. This contraction increased in a Ca concentration-dependent manner and reached a maximum at 2 mM Ca. The basal tone of aorta in SHR was suppressed by verapamil $(10^{-6}M)$. The basal tone of aorta in SHR increased about 50% in the strips of endothelial rubbing, compared with that of intact endothelium. Basal $^{45}Ca$ uptake in the aortic single smooth muscle cells of SHR was greater than that of WKY (p<0.01), Specific bindings of $[^3H]nitrendipine$ in the aortic single smooth muscles of SHR and WKY were saturable. The dissociation constant $(K_d)\;was\;0.71{\pm}0.15\;and\;1.18{\pm}0.08nM$ SHR, respectively, and the difference in $K_d$ between two strains was statistically significant (p<0.03). The maximal binding capacity $(B_{max})\;was\;34.6{\pm}3.2\;and\;47.4{\pm}4.3\;fmol/10^6$ SHR respectively, and the difference of $(B_{max})$ between two strains was statistically significant (p<0.05). from the above results, it is suggested that the increase of Ca influx via potential-operated Ca channels and the increase of the number of dihydropyridine-sensitive Ca channels contribute to high basal tone of the aortic strips in SHR.