• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.51-56
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• 1996

The objectives of this study is to find out mechanism of vasodilating effects of ANP in 2K-1C renovascular hypertensive rat aorta and to compare with those of normotensive rat aorta. In 2K-1C renovascular hypertensive rat, average arterial blood pressure and plasma renin activity were higher than in normotensive rat. In 2K-1C renovascular hypertensive rat aorta, NE sensitivity was more increased and maximal contraction of aorta by NE was higher than those of normotensive rat aorta. ANP inhibited NE-induced contraction in both 2K-1C renovascular hypertensive and normotensive rat aorta, concentration-dependently. However, ANP was less effective for relaxing NE-induced contraction in 2K-1C renovascular hypertensive rat aorta than in normotensive rat aorta. ANP inhibited $^{45}Ca^{2+}$ uptake induced by NE in both 2K-1C renovascular hypertensive and normotensive rat aorta. From these results. inhibition of $Ca^{2+}$ influx may be one of the vasodilating mechanism of ANP in 2K-1C renovascular hypertensive rat aorta. Although the potency of ANP in relaxing NE-induced contractions was attenuated, the efficacy of ANP was not changed in 2K-1C renovascular hypertensive rat aorta compared with that of ANP in normotensive rat aorta. Abbreviations: ANP, Atrial natriuretic peptide; 2K-1C, 2-kidney 1 clip; NE, norepinephrine; SHR, Spontaneously hypertensive rat; DOC, Deoxycorticosterone; EDTA, Ethylenediaminetetra-acetic acid; PSS, Physiological salt solution; TRIS, tris(hydroxymethyl) aminomethane

• The Korean Journal of Physiology
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• v.15 no.1
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• pp.19-25
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• 1981

The present study was undertaken to investigate the effect of ascorbic acid on the blood pressure of SHR in established phase. Twenty SHR at age of 23 weeks were divided into two groups; The control group and the ascorbic acid group in which 3 mg/kg/day ascorbic acid was orally administered for 10 weeks. The results obtained were as follows; 1) In the control group the systolic pressure($192.7{\pm}4.2\;mmHg$ at O week) tended to increase gradually throughout the entire experimental period. 2) In the experimental group the systolic pressure($193.5{\pm}3.5\;mmHg$ at O week) was generally lower as compared with that of control group. A significant difference in the blood pressure was observed between two groups at 3 rd and 4 th week of experimental period. Though it is impossible from the result of present study to elucidate the exact mechanism of blood pressure lowering effect of ascorbic acid, it is inferred that ascorbic acid may exert its effect at the vascular walls.

• Journal of Microbiology and Biotechnology
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• v.14 no.6
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• pp.1318-1323
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• 2004

This study describes the purification and characterization of a novel antihypertensive angiotensin 1­converting enzyme (ACE) inhibitory peptide from Saccharomyces cerevisiae. Maximal production of the ACE inhibitor from Saccharomyces cerevisiae was obtained from 24 h of cultivation at $30^{\circ}C$ and its ACE inhibitory activity was increased by about 1.5 times after treatment of the cell-free extract with pepsin. After the purification of ACE inhibitory peptides with ultrafiltration, Sephadex G-25 column chromatography, and reverse-phase HPLC, an active fraction with an $IC_{50}$ of 0.07 mg and $3.5\%$ yield was obtained. The purified peptide was a novel decapeptide, showing very low similarity to other ACE inhibitory peptide sequences, and its amino acid sequence was Tyr-Asp-Gly-Gly-Val-Phe-Arg-Val-Tyr-Thr. The purified inhibitor competitively inhibited ACE and also showed a clear antihypertensive effect in spontaneously hypertensive rats (SHR) at a dosage of 1 mg/kg body weight.

• Journal of Microbiology and Biotechnology
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• v.16 no.5
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• pp.757-763
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• 2006

Angiotensin I-converting enzyme (ACE) inhibitors have generally been very useful to remedy or prevent hypertension. This study describes the extraction and characterization of an ACE inhibitor from the fruiting body of Pholiota adiposa ASI 24012, which can be used as an antihypertensive drug. The maximal ACE inhibitory activity $(IC_{50};0.25mg)$ was obtained when the fruiting body of Pholiota adiposa ASI 24012 was extracted with distilled water at $30^{\circ}C$ for 12 h. After the purification of ACE inhibitor with ultrafiltration, Sephadex G-25 column chromatography, and reverse-phase HPLC, an active fraction with an $IC_{50}$ of 0.044 mg was obtained. The purified ACE inhibitory peptide was a novel pentapeptide, showing very little similarity to other ACE inhibitory peptide sequences. The molecular mass of the purified ACE inhibitor was estimated to be 414 daltons with a sequence of Gly-Glu-Gly-Gly-Pro, and showed a clear antihypertensive effect on spontaneously hypertensive rats (SHR) at a dosage of 1 mg/kg.

• Journal of Haehwa Medicine
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• v.14 no.2
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• pp.55-70
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• 2005

In oriental medicine, Gamibangpungtongsungsan (KBTS) has been used as a therapeutic agent for the treatments of acute stage of cerebrovascular diseases and hypertension. In the present study, underlying mechanism on KBTS effects was investigated using spontaneously hypertensive rats (SHR) by determining related parameters such as blood pressure, heart-beat rates, and hormones and plasma constituents. The major finding are summarized as follows. 1. KBTS treatment at concentrations lower than $125\;{\mu}g/m{\ell}$ did not show any cytotoxicity on cultured human fibroblast cells. 2. KBTS treatment in SHR significantly decreased blood pressure and heart-beat rate compared with untreated control. 3. KBTS treatment in SHR decreased aldosterone levels in the blood compared with untreated control, but the difference was not statistically significant. 4. KBTS treatment in SHR significantly decreased dopamine, norepinephrine and epinephrine levels in the blood compared with untreated control. 5. KBTS treatment in SHR decreased plasma ion concentrations such as Na+, K+, Ca2+, Cl- compared with untreated control; decreases in Na+ and Cl- were statistically significant. 6. KBTS treatment in SHR significantly decreased TNF-$\alpha$, IL-6, and IL-10 levels in the blood compared with untreated control. Thus, the present data show evidence on anti-hypertension activity of KBTS in an experimental animal system, which can provide further insights into the development of anti-hypertension therapeutic agents.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.46-46
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• 2003

The present study examined the effect of alcohol extract of Isaria sinclairii on blood pressure in spontaneously hypertensive rats (SHR). The blood pressure and heart rate were measured after treatment of alcohol extract of Isaria sinclairii by indirect tail cuff method and direct in vivo model. Male SHR were treated with extracts for 2 or 4 weeks starting at 12 weeks of age. (omitted)

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.9
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• pp.1369-1373
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• 2003

ACE (Angiotensin-I converting enzyme) inhibitory peptides derived from foods are thought to suppress high blood pressure by inhibiting ACE. We tried to make efficient production of the ACE inhibitory hydrolysate from egg albumen. A hydrolysate digested by neutrase presented the highest ACE inhibitory activity ($IC_50\;value=256.35{\mu}g/ml$) and the proper proteolysis was occurred by 1.0% enzyme addition and 4 h incubation at $47^{\circ}C$. Antihypertensive effect of neutrase hydrolysate was investigated in spontaneously hypertensive rats (SHR, n=5). Systolic blood pressure (SBP) was decrease by 6.88% (-14.14 mmHg, p<0.05) at 3 h after oral administration of 300 mg/kg body weight, and by 13.33% (-27.72 mmHg, p<0.05) by emulsified hydrolysate. These results showed that it is very effective to utilize egg albumen as a protein source for the production of ACE inhibitory peptides. However, further studies are required to investigate the methods to increase recovery yield and the isolation of active peptide is necessary for determining its sequence responsible for ACE inhibitory activity.

• The Korean Journal of Physiology
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• v.16 no.2
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• pp.137-146
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• 1982

The present study was undertaken to find out fasting total plasma cholesterol levels of SHR at different phases(labile, established and malignant) in the course of hypertension development and also to investigate effect of nicotine on plasma cholesterol levels of these animals. In nicotine administered group, 2.18 mg/kg nicotine was given daily for six weeks. The results obtained are as follows; 1) Mean total plasma cholesterol levels of SHR at labile, established and malignant phases were $104.6{\pm}3.1\;mg/dl$, $120.8{\pm}2.6\;mg/dl$ and $136.6{\pm}2.5\;mg/dl$ respectively. The total plasma cholesterol level generally increased with age of experimental animals. 2) After administration of nicotine (2.18 mg/kg/day) for six weeks, mean total plasma cholesterol levels of SHR at labile, established and malignant phases were $130.2{\pm}3.1\;mg/dl$, $150.4{\pm}3.3\;mg/dl$ and $166.6{\pm}3.2\;mg/dl$, respectively. The result of present study strongly suggests that nicotine has a positive relationship with plasma cholesterol levels in SHR.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.138-144
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• 2004

Therapeutic effect of a Kampo medicine, Choto-san, in patients with vascular dementia was demonstrated by a double-blind and placebo-controlled clinical trial. To clarify the therapeutic efficacy of Choto-san, anti-ischemic effect in mice, hypotensive effect in spontaneously hypertensive rats (SHR), anti-oxidative effects in vitro, and N-methyl-D-aspartate (NMDA) receptor-blocking activity using Xenopus oocytes were studied. (1) Pretreatment with Choto-san (0.75-6.O g/kg, P.O.) or a component herb Chotoko (Uncaria genus: 75 - 600 mg/kg, P.O.) prevented ischemia-induced impairment of spatial learning behaviour in mice. Indole alkaloids- and phenolic fractions extracted from Chotoko also improved significantly the learning deficit. (2) Subchronic administration of Choto-san (0.5 g/kg, p.o.) caused a significant hypotensive effects in SHR. (3) Choto-san, Chotoko, and the phenolic constituent, (-) epicatechin, significantly protected the NG108-15 cell injury induced by $H_20_2$ exposure in vitro and also inhibited lipid peroxidation in the brain homogenate. (4) Indole alkaloids, rhynchophylline and isorhynchophylline (1-100 uM), reversibly reduced NMDA-induced current in the receptor-expressed Xenopus oocytes. These results suggest that anti-vascular dementia effects of Choto-san are mainly due to the effect of Chotoko. From these results, it is possible to make a novel dietary supplement through several extraction steps from Chotoko.

• Korean Journal of Pharmacognosy
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• v.36 no.1 s.140
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• pp.17-20
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• 2005

We previously reported that the exogenous administration of cumambrin A, a sesquiterpene lactone from the dried flowers of Chrysanthemum boreale Makino has a pharmacological effect on normalization of blood pressure in the spontaneously hypertensive rats (SHR). In the present study, we further investigated the effect of cumambrin A on the relaxation of phenylephrine-induced precontracted rat aortic artery rings. The potency of cumambrin A was than compared to verapamil, a well known $Ca^{2+}-channel$ blocker. The results demonstrate that the isolated rat aortic arteries are relaxed to basal tension at a concentration of $5{\times}10^{-5}\;M$ cumambrin A treatment. The results also show that the phenylephrine-induced contraction is inhibited by a pretreatment of cumambrin A. Co-treatment of cumambrin A and verapamil showed a strong synergetic effect on the relaxation of rat aortic artery rings. Thus, these data demonstrate that cumambrin A is a potent relaxant of rat aortic smooth muscle and suggest that cumambrin A modulates intracellular or extracellular $Ca^{2+}$ mobilization.