• 대한한의학방제학회지
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• 제10권1호
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• pp.113-129
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• 2002

The present study designed to investigate whether hwangryunhaedok-tang show an anti-hypertensive effect and elucidate its possible mechanism in spontaneously hypertensive rats. The systolic blood pressures (SBP) were significantly decreased as an oral administration of hwangryunhaedok-tang compared with their control group. The urine volume was significantly increased by administration of hwangryunhaedok-tang but urinary sodium (UNaV), potassium (UKV), chloride excretion (UCIV) were not remarkably affected. The urinary creatinine excretion rate (UcrV) was significantly increased in rats administered with hwangryunhaedok-tang in association with increase of creatinine clearance (Ccr). The urine osmolality (Uosmol) was significantly decreased in SHR administered with hwangryunhaedok-tang without being changed in solute-free water reabsorption ( TcH20). The expressions of Aquaporin 2 (AQP-2). 3 and ${\alpha}\;1$, ${\beta}\;1$ subunits of Na.K-ATPase were determined by Western blot analysis to assess the role of these proteins in association with changes of renal functions in SHR administered with hwangryunhaedok-tang. The expression of AQP-2 and 3 protein was significantly down-regulated in the kidney of SHR administered with hwangryunhaedok-tang compared with those in control rats without being altered expression of ${\alpha}\;1$, ${\beta}\;1$ subunits of Na,K-ATPase. In the in vitro assay, Angiotensin converting enzyme (ACE) was inhibited by hwangryunhaedok-tang in a dose-dependent manner. Berberine and/or palmatine, which are well known as a main components of hwangryunhaedok-tang, also have an ACE inhibitory effects in a dose-dependent manner. Taken together, these results suggest that hwangryunhaedok-tang lowered blood pressure through the increase of diuresis caused by down-regulation of water channels and the inhibition of Angiotensin converting enzyme.

• 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.

• 한국감성과학회:학술대회논문집
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• 한국감성과학회 2009년도 춘계학술대회
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• pp.97-100
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• 2009

The purpose of this study was to examine effects of treadmill running training on superoxide product of spontaneously hypertensive rats. 20 males aged five week old rats were used for the experiments. They were randomly selected into experimental group (10 rats) and control group (10 rats) after being housed in laboratory for two weeks. The rats of experimental group performed treadmill exercise from 15 minutes for the first time to 35 minutes for the last one in order to familiar with experimental protocol ($VO_{2}max\;65{\sim}70%$, 0.9km/h, 5 times/week, 35 minutes/session). They began to perform treadmill running at the age of eight weeks for eight weeks. Superoxide production and NADPH oxidase activities were measured on the aortal from end of experiment. All statistical analyses and description methods were computed by SPSS Version 10.0. Differences in the values between experimental group and control group were calculated using t-tests. The results of this study were: there wewe no significant differences in superoxide production, NADPH oxidase-drivened superoxide activity, NADPH oxidase activity between two groups (p>.05). Spontaneously hypertensive rats of experimental group were characterized by higher superoxide production and lower NADPH oxidase-drivened superoxide activity and NADPH oxidase activity in comparison with the control group. One possible explanation of this finding was that NADPH oxidase activity of experimental group was lower than the control group. It can be concluded that treadmill running for eight weeks was associated positively with superoxide product of spontaneously hypertensive rats.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.154-155
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• 1998

Taurine, 2-aminoethanesulfonic acid is widely distributed in animal tissues and has a variety of biological activities. A recent worldwide study demonstrated beneficial effects of taurine on aging and age-associated disorders. In general, taurine levels in the brain decrease when an animal is subjected to pathologic conditions such as ischemia-anoxia and seizure. But taurine levels tend to increase in the brain in hypertention. In the present study, the blood-brain barrier BBB) transport of [$^3$H]taurine was compared between spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley rats (SD) using Internal artery carotid perfusion (ICAP) at a rate of 4$m\ell$/min for 10, 15 and 30 second. Calculated V$\_$D/, volume of distribution in brain, and PS, the permeability surface area product of [$^3$H]taurine through the BBB in SHR was a little lower than that in SD. PS for 15s is more higher than that of other seconds in both of them. It could be followed by taurine efflux back into blood after 15s. We also obtained pharmacokinetic parameters using intravenous injection of plasma volume marker, [$\^$14/C]sucrose and [$^3$H] taurine. PS value of [$^3$H]taurine in SHR (16.1 ${\pm}$ 2.9 ${\times}$ 10$\^$-3/ $m\ell$/min/g) was significantly higher than that in SD (7.4 ${\pm}$ 0.8 ${\times}$ 10$\^$-3/ $m\ell$/min/g). There is also significant difference for %ID/g in brain between SHR (0.195 ${\pm}$ 0.031) and SD (0.058 ${\pm}$ 0.003).

• Archives of Pharmacal Research
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• 제14권3호
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• pp.242-248
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• 1991

Antihypertensive effect of YH 334 was examined in various experimental hypertension rat models and the systemic and regional hymohynamic profiles of the compound were investigated in conscious spontaneously hypertensive rats (SHR). The antiypertensive potensive potency of YH 334 is found to be more than 10 times stronger than that of nitrendipine in the all hypertensive models. The effective doses to lower the initial blood pressure by 20% $(ED_{20})$ of YH334 were 1.4 mg/kg in normotensive rats (NR), 0.7 mglkg in SHR. 0.1 mg/kg in DOCA salt hypertensive rats (DHR) and 0.4 mg/kg in renal hypertensive rats (RHR), and the $ED_{20}$ values of nitrendipine were 15.8 mg/kg in NR, 7.1 mg/kg in SHR, 1.7 mg/kg in DHR and 4.8 mg/kg in RHR. The primary hemodynamic effect hemodynamic profile is similar to that of nitrendipine. Both compounds seem to produce potent antihypertensive effects by lowering peripheral resistance in the skeletal muscles. In the organ bath study using isolated rabbit aorta, YH 334 was found to be a potent voltage dependent calcium channel blocker without significant inhibitory effect on the receptor operated calcium channels like the most of other dihydropyridine type calcium antagonists. Furthermore, YH334 showed acute diuretic and natriuretic effects in conscious SHR, which may render the unnecessary restriction of sodium in the diet of those patients on long term hypertension therapy. This effect would provide an additional benefit to its potent antihypertensive activity.

• 약학회지
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• 제26권2호
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• pp.105-110
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• 1982

The antihypertensive effect of clonidine administered concurrently with labetalol or metoprolol were studied with spontaneously hypertensive rats (SHR). The changes of heart rate were also observed in the same rats. Every drug was orally administered single dose after prechecking the systolic blood pressure and heart rate of SHR. The blood pressure of SHR in concurrently administered group was more significantly decreased than in alone administered group. The effective and stable decrease of blood pressure was maintained at the group of clonidine with labetalol (0.05+50mg/kg) for 9 hours. The group of clonidine with metoprolol (0.05+100mg/kg) manifested more marked decrease of blood pressure than the group of metoprolol (100mg/kg) alone for 9 hours. The diminishing effect of heart rate was enhanced in group of administering clonidine with labetalol, decreasing the dose of labetalol from 50mg/kg via 25mg/kg to 12.5mg/kg. On the other hand, in the group that clonidine was administered concurrently with metoprolol, the diminishing effect of heart rate was decreased with decreasing doses of metoprolol from 100mg/kg via 50mg/kg to 25mg/kg.

• 대한약리학회지
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• 제30권1호
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• pp.75-86
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• 1994

선천성 고혈압 흰쥐(SHR)와 정상혈압 흰쥐에서 교감신경성 신경전달에 미치는 부신수질 및 renin-angiotensin계의 역할을 알아보기 위해, 부신수질을 제거하거나 angiotensin 변환 효소 억제제를 장기간 처치한 뒤 중추신경계가 파괴된 상태에서 절전신경을 자극했을 때 나타나는 승압반응과 대동맥의 catecholamine농도 및 angiotensin 변환 효소 활성도의 변화를 비교 검토하였다. 부신수질을 제거하더라도 중추신경계를 파괴하기 전후의 혈압에는 영향을 주지 못했으며, 절전 신경 자극에 의한 승압반응은, 자극 주파수에 의존적으로 증가하였으며 prazosin 전처치로서 거의 완전히 억제되었다. 정상혈압 흰쥐에서와는 달리, 선천성 고혈압 흰쥐에서는 부신수질을 제거했을 때는 절전신경 자극에 의한 승압반응이 부신수질을 제거하지 않는 군(이하 대조군)에 비하여 유의하게 약화되었다. SHR에서 부신수질 제거로 부신 catecholamine 함량은 현저히 감소되었고, 혈청의 angiotensin 변환 효소 활성도는 감소되는 경향을 나타내었다. 그러나 혈장 및 대동맥 절편의 catecholamine 함량, 대동맥 절편의 angiotensin 변환 효소의 활성도는 대조군과 유의한 차이가 없었다. 그러나 WKY에서는 부신수질이 제거된 군에서 대동맥 절편의 angiotensin 변환 효소의 활성도와 catecholamine함량이 대조군에 비해 유의하게 증가되어 있었다. Enalapril처치에 의해서 선천성 고혈압 흰쥐 평균 혈압은, 부신 catecholamine 함량 및 대동맥 절편의 angiotensin 변화 효소의 활성도와 함께 현저히 저하되어 정상혈압 흰쥐와 유사하였다. 그리고 선천성 고혈압 흰쥐에서 부신수질의 제거로 절전신경 자극에 의한 승압반응이 대조군에 비하여 약화되는 현상은 enalapril을 처치하였을 때는 관찰되지 않았다. 이상의 결과로 미루어보아 교감신경성 신경전달을 항진시키는 부신수질의 작용은 renin-angiotensin계의 활성화에 의존적이었으며, 부신수질의 제거로 정상혈압 흰쥐에서는 renin-angiotensin계가 보상적인 조절이 일어났으나, 선천성 고혈압 흰쥐에서는 보상적인 조절이 일어나지 않았다.

• Journal of Acupuncture Research
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• 제20권2호
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• pp.123-134
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• 2003

Objective : This experimental in vitro study investigates the effects of electro acupuncture stimuli to the DCX and PSA-NCAM positive cells in the dentate gyrus of spontaneously hypertensive rats. Methods : We used immunohistochemical methods to observe the change of neuron cells, and then counts the immunoactive cells under the $100{\times}$ visual field optical microscope. Results : 1. The counts of DCX-positive cells in the dentate gyrus significantly increased in the 2Hz group versus control group. Otherwise 100Hz group did not have a significant differance. 2. The counts of PSA-NCAM-positive cells in the dentate gyrus rather decreased in the both 2Hz group and 100Hz group versus control group. Conclusions : We find out the electro acupuncture stimuli have some effects upon cerebral neuron cell in the dentate gyrus spontaneously hypertensive rats.

• The Korean Journal of Physiology
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• 제27권2호
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• pp.217-225
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• 1993

The role of endogenous brain angiotensin ll (Ang ll) in mediating the cardiovascular and vasopressin responses to hemorrhage was assessed in conscious spontaneously hypertensive rats (SHR), and normotensive Wistar-Kyoto (WKY) rats. Artificial cerebrospinal fluid (aCSF) with or without losartan (DuP 753), a specific Ang ll receptor subtype I $(AT_1)$ antagonist and saralasin, a combined $AT_1/AT_2$ antagonist was administered into the cerebral lateral ventricle. Hemorrhage was performed at a rate of 3 ml/kg/min far 5 min. Intracerebroventricular administration of losartan and saralasin had no effect on the basal blood pressure. However, in response to acute hemorrhage, central Ang ll antagonists produced a remarkably greater fall in blood pressure, a reduced tachycardia, and an enhanced renin release compared with the aCSF control experiment in SHR, but effected no significant change in WKY rats. Central Ang ll-blocked SHR showed significantly lower blood pressure and heart rate during the recovery period than the aCSF control rats. Vasopressin release tallowing the hemorrhage was attenuated by icv Ang ll antagonists: the effect was more pronounced in SHR than in WKY rats. Centrally administered losartan and saralasin produced remarkably similar effects on the cardiovascular function and vasopressin responses to hemorrhage. These data suggest that brain Ang ll acting primarily through AT, receptors plays an important physiological role in mediating rapid cardiovascular regulation and vasopressin release in response to hemorrhage especially in Hypertensive rats.

• 대한한방내과학회지
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• 제32권3호
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• pp.345-360
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• 2011

Objectives : This study was examined to investigate the effects of Cheonmagudeng-um gagam (CGG) extract on spontaneous hypertension. Methods : For the study of CGG, we divided rats into three groups. The normal group was Wister Kyoto rats (WKY). The control group was spontaneously hypertensive rats (SHR). The treatment group was SHR which were administered CGG extract (SHR-CGG). SHR-CGG were orally administered CGG extract that was diluted in distilled water at the various concentrations for 4 weeks (234.5 mg/kg) and SHR were orally administered the same dosage of plain distilled water as SHR-CGG. Then we measured anti-oxygen effects, ACE inhibitory activity, weight of heart and kidney, blood pressure, heart rate, plasma aldosterone, electrolyte, creatinine, uric acid, BUN, and observed the cortex of the cardiac muscle, kidney, and adrenal gland. Results : CGG increased DPPH scavenging activity and SOD similar activity depending on the concentration. CGG significantly decreased ROS, TNF-${\alpha}$, IL-6, IL-$1{\beta}$, heart weight, blood pressure, heart rate, aldosterone, and BUN in SHR. CGG increased ACE inhibition activity depending on the concentration. CGG inhibited the heart, kidney and adrenal gland tissue injury that is caused by hypertension. Conclusions : These results suggest that CGG is effective in treatment and prevention of hypertension.