• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.19-24
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• 2004

The vascular relaxant effect of amlodipine adipate, a new salt of amlodipine, was evaluate in isolated rat aorta, and compared with that of amlodipine besylate. Furthermore, antihypertensive effects were measured in hypertensive rat models, such as spontaneously hypertensive rats (SHR) and rena1 hypertensive rats (RHR). Amlodipine adipate concentration-dependently inhibited $Ca^{2+}$-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5 h;$IC_{50}$: 3.76 nM), having a pattern and a potency similar to those of amlodipine besylate ($IC_{50}$: 4.01 nM). In SHR and RHR, orally administered amlodipine adipate produced a dosedependent and long-lasting (>10-24 h) antihypertensive effect ($ED_{20}$: 2.48 and 1.57 mg/kg, respectively), with a pattern and a potency similar to those of amlodipine besylate ($ED_{20}$: 2.50 and 1.99 mg/kg in SHR and RHR, respectively). These results suggest that amlodipine adipate is a potent and long-lasting antihypertensive agent and that its antihypertensive effect is not significantly different to that of amlodipine besylate.

• Biomolecules & Therapeutics
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• v.8 no.2
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• pp.194-198
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• 2000

Taurine, 2-aminoethanesulfonic acid is widely distributed in animal tissues and has a variety of bio-logical activities. A recent worldwide study demonstrated beneficial effects of taurine on aging and age-associated disorders. In general, taurine levels in the brain decease when an animal is subjected to pathologic conditions such as ischemia-anoxia and seizure. But the taurine levles tend to increase in the brain in hypertensive state. 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 intravenous injection technique in vivo. We also obtained pharmacokinetic parameters of plasma volume maker, [$^{14}$ C] sucrose and [$^3$H]taurine after inject to rats simulatenously. BBB permeability surface area product (PS) value of [$^3$H]taurine in SHR (16$\pm$2.9$\times$10$^{-3}$ ml/min/g) was significantly higher than that in SD (7.4$\pm$0.8$\times$10$^{-3}$ ml/min/g). There is also significant difference for brain uptake of [$^3$H]taurine between SHR (0.195$\pm$0.031%ID/g) and SD (0.058$\pm$0.003% ID/g). This is due to difference of area under the plasma concentration-time curve (AUC) and that of total clearance (Class) between SHR and SD. No significant difference was indicated from other organ uptakes such as lung, heart, liver SHR and SD. But also kidney uptake was much higher in SHR. In conclusion, [$^3$H]taurine in plasma was slowly eliminated in SHR than in SD and uptake of [$^3$H]taurine in SHR is much higher than that of SD. This results suggest increased taurine level in the brain in hypertension state have an any effect on the brain uptake of taurine.

• YAKHAK HOEJI
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• v.30 no.6
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• pp.334-342
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• 1986

The relationship between the maintenance of hypertension and the central noradrenergic nervous system activity in spontaneously hypertensive rats (SHR) was studied. The norepinephrine turnover rates in 5 brain areas; telencephalon, hypothalamus/thalamus, midbrain, pons/medulla, cerebellum as a measure of noradrenergic neuronal activity were measured at the ages of 14 weeks in SHR and normotensive Wistar rats. In 14-week old SHR, blood pressure was significantly higher than in normotensive rat, and central norepinephrine turnover rates were significantly greater in telencephalon, hypothalamus/thalamus, midbrain. There were no differences between norepinephrine turnover rates in pons/medulla, cerebellum of SHR and those of normotensive rats.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.125-132
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• 1997

Our previous study showed that in vivo treatment of spontaneously hypertensive rats (SHR) with protopanaxatriol ginsenosides (PPT) reduces the blood pressure and inhibits the con- tractions induced by endothelium-derived contracting factor (prostaglandin endoperoxide ($PGH_2$) and superoxide anion) in aorta isolated from SHR. The aim of the present study is to examine whether PPT improves endothelial functions in the isolated thoracic aorta of SHR in vitro. Treatments of aortic rings with PPT, purified ginsenoside $Rg_1$ ($Rg_1$) or indomethacin normalized endotheliuln-dependent relaxation to acetylcholine, but not with protopanaxadiol ginsenosides (PPD) and purified ginsenoside Rb1 (Rb1). The effects of PPT were dose-dependent. PGH,- and oxygen free radical-inducted contractions in rat aorta without endothelium were inhibited by PPT or $Rg_1$, but not by PPD or $Rb_1$. Contractions induced by PGF2$\alpha$, U-46619, a stable thromboxane A2 agonist or KCI (60 mM) were not inhibited by PPT, $Rg_1$ or $Rb_1$. These findings demonstrate that PPT but not PPD scavenges the oxygen-derived free radicals and/or antagonize the effects of $PGH_2$ in the vascular smooth muscle and may explain the hypotensive effect of ginseng in the SHR.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.57-61
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• 2002

The renoprotective activities of white ginseng radix and rootlet were compared in spontaneously hypertensive rat (SHR) with diabetes. During oral administration of white ginseng radix (Ginseng Radix Alba, GRA) and white ginseng rootlet (Ginseng Radix Palva, GRP) for four weeks, arterial blood pressure and blood glucose levels were determined at every 10 days. In both GRA- and GRP-treatment groups, arterial blood pressures started to go down after 10 days of administration and maintained throughout the study period. After four weeks administrations of GRA and GRP, diastolic blood pressures were significantly decreased with 17% and 9%, respectively. GRA treatment also decreased blood glucose levels after 10 days of administration when compared with diabetic SHR group. At the end of the experiment, serum creatinine (Scr) and blood urea nitrogen (BUN) were not significantly different between the groups, except 62% higher value of BUN in diabetic SHR group when compared with SHR group. In the diabetic SHR group, the excretion of urinary albumin was increased significantly when compared with SHR. The level of urinary albumin in GRA treated group was markedly reduced when compared with diabetic SHR group $(67.8{\pm}4.7\;vs.\;131.3{\pm}13.5\;mg/24\;h).$ To examine the effects of ginseng radices on an overt diabetic nephropathy, index of kidney hypertrophy and transforming growth $factor-{\beta}1\;(TGF-{\beta}1)$ protein levels were evaluated. The glomerular and tubular cells stained positive for $TGF-{\beta}1$ seemed to be more abundant in diabetic SHR than in those with SHR, and GRA treated rats showed somewhat less $TGF-{\beta}1$ protein in glomerular and tubular cells when compared with diabetic SHR. Our results suggest that GRA might be a useful antihypertensive and antidiabetic agent with renoprotective effect.

• Journal of Nutrition and Health
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• v.22 no.2
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• pp.91-101
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• 1989

This study was performed to investigate the effects of different dietary magnesium levels on systolic blood pressure and mineral distribution in normotensive and spontaneously hypertensive rats. In experiment 1, Normotensive rats(NTR ; Sprague Dawley, Female) were given diets containing regular magnesium (0.05% Mg ; rMg), marginal magnesium (0.01% Mg ; mMg) or marginal magnesium with stress(0.01% Mg + stress ; mMg + Str). In experiment 2, spontaneously hypertensive rats (SHR ; Kyoto Wistar, Femal) were fed diets containing regular magnesium(0.05% Mg ; rMg) and high magnesium (0.2% Mg ; hMG). The following were found ; 1) NTR treated with marginal magnesium with stress showed significant increase in systolic blood pressure (SBP). Marginal magnesium diet without stress resulted in nonsignificant increase in SBP. Significant in crease of blood pressure showed in NTR treated with marginal magnesium and stress was associated with decreased magnesium and increased calcium content in femur, reticulocyte and plasma. 2) In experiment 2, magnesium supplementation to SHR showed significant attenuation of their systolic blood pressure with increasing age. The attenuation of SBP showed in SHR was associated with increased magnesium, lowered calcium content in cardiac muscle and reticulocyte and decreased plasma sodium and aldosterone level.

• Journal of Nutrition and Health
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• v.35 no.8
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• pp.840-847
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• 2002

This study explored the effect of dietary levels of Na and Ca on spontaneously hypertensive rats (SHR). SHR were randomly divided into 5 groups and fed a high fat/cholesterol diet containing three levels of Na (0.05, 0.1, 1.5%) and Ca (0.1, 0.5, 1.5%) for 9 weeks. Body weight gain was not influenced by dietary intake but water intake significantly increased in high Na supplementation. Systolic blood pressure was not influenced by dietary Na and Ca levels but was decreased by dietary low Na/high Ca levels at 9 weeks. Angiotensin-II level was affected by dietary Na level but not by Ca levels. Plasma Ca, Mg, K and Na levels were in the normal range regardless of dietary Na and Ca levels. Weight, and K and Na contents of the heart and kidney were not significantly different among those with different dietary Na and Ca levels. Ca and Mg contents of the heart and kidney were significantly higher in the normal Na/normal Ca group. Ca and Mg in the feces were higher in those with high Ca intake. Na in the feces was higher in those with high Na intake. Therefore, Na and Ca had different mechanisms in the hypertension/hyperlipidemia models, respectively. And we suggested that Mg must be supplemented when Ca intake was high because Mg excretion was increased by Ca supplementation.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.554-568
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• 2010

Objective : This study was examined to investigate the effect of Gamitongseong-san(GTS) extract on spontaneous hypertension. Methods : After administering GTS extract to SHR for 4 weeks, we measured anti-oxygen effects, weight of body, heart and kidney, blood pressure, heart rate, aldosterone, catecholamine, electrolyte, uric acid, and BUN. Results : 1. GTS increased 2,2-diphenyl-1-picrylhydrazyl(DPPH) scavenging activity and superoxide dismutase(SOD) similar activity depending on the concentration. 2. GTS significantly decreased heart weight in spontaneously hypertensive rat. 3. GTS significantly decreased blood pressure and heart rate in SHR. 4. GTS significantly decreased aldosterone. 5. GTS significantly decreased norepinephrine and epinephrine. 6. GTS significantly decreased $K^+$. 7. GTS significantly decreased BUN. Conclusions : These results suggest that GTS may be usefully applied for the treatment of hypertension.

• Archives of Pharmacal Research
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• v.12 no.2
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• pp.128-134
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• 1989

$Na^+-Ca^{2+}$ exchange process in sarcolemmal vesicles isolated from mesenteric arteries of Wistar-Kyoto normotensive(WKY) and spontaneously hypertensive rats(SHR) was investigated. The sarcolemmal fractions isolated after homogenization and sucrose density gradient centrifugation were enriched with 5'-nucleotidase and ouabain sensitive, $K^+-dependent$ phosphatase activities. When the vesicles were loaded with $Na^+$, a time dependent $Ca^{2+}$ uptake was observed. However, very little $Ca^{2+}$ uptake was observed when the vesicles were loaded with $K^+$, or $Ca^{2+}$ uptake of the $Na^+-loaded$ vesicles was carried out in high sodium medium so that there was no sodium gradient. When the vesicles loaded with $Ca^{2+}$ by $Na^+-Ca^{2+}$ exchange were diluted into potassium medium containing EGTA, $Ca^{2+}$ was rapidly released from the vesicles. $Na^+-dependent\;Ca^{2+}$ uptake was increased in SHR compared to WKY, but passive efflux of preaccumulated $Ca^{2+}$ from the vesicles was decreased in SHR. The data indicate that the membrane vesicles of rat mesenteric arteries exhibit $Na^+-Ca^{2+}$ exchange activity. It is also suggested that changes of this process in vascular smooth muscle cell membrane of SHR may be involved in higher intracellular $Ca^{2+}$ concentration and higher basal tone in SHR.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.537-544
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• 2005

We have examined distribution and expression of caveolin-3 (cav-3), one of three caveolin isoforms from 16-wks-old spontaneously hypertensive rats (SHR) compared with age-matched control wistar-kyoto (WKY) rats. The expression of cav-3 was increased, whereas expression of PKB/Akt and calcineurin (Cn) was not changed in cardiac tissues of SHR compared to WKY rats. Interestingly, expression of cav-3, PKB/Akt and Cn were decreased in plasma membrane fraction in SHR compared to WKY rats. In H9c2 cardiomyoblast cells treated with phenylephrine ($50{\mu}M$, 48hr) or isoproterenol ($10{\mu}M$, 48hr), the expression of cav-3 was markedly enhanced compared to nontreated cells. Upon immunofluorescence analysis, cav-3 was localized in plasma membrane of control H9c2 cells. However phenylephrine or isoproterenol treatment caused translocation of cav-3 to perinuclear region. These results suggest that cav-3 plays as positive regulators in the development of hypertrophy in cardiac tissues of SHR rats.