• Title/Summary/Keyword: Antihypertensive

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Pharmacological Profile of KR-31125, an Orally Active AT1 Receptor Antagonist (안지오텐신 수용체 리간드 KR-31125의 생체 내 활성에 관한 연구)

  • Lee, Sung-Hou
    • Journal of Life Science
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    • v.20 no.7
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    • pp.969-976
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    • 2010
  • In vivo studies of KR-31125 (2-butyl-5-dimethoxymethyl-6-phenyl-7-methyl-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine) were performed in pithed rats, conscious angiotensin II (AII) challenged normotensive rats, renal hypertensive rats (RHRs) and furosemide-treated beagle dogs. KR-31125 induced a non-parallel right shift in the dose-pressor response curve to AII ($ID_{50}$: 0.095 mg/kg) with a dose-dependent reduction in the maximum responses in pithed rats. Compared to losartan, this antagonistic effect was about 18 times more potent, presenting competitive antagonism. Other agonists such as norepinephrine and vasopressin did not alter the responses induced by KR-31125. Orally administered KR-31125 had no agonistic effect and dose-dependently inhibited the pressor response to AII with a slightly weaker potency ($ID_{50}$: 0.25 and 0.47 mg/kg, respectively) in the AII-challenged normotensive rat model, but with a more rapid onset of action than losartan (time to $E_{max}$: 30 min for KR-31125 and 6 hr for losartan). KR-31125 produced a dose-dependent antihypertensive effect with a higher potency than losartan in RHRs, and these effects were confirmed in furosemide-treated dogs where they presented a dose-dependent and long-lasting (>8 hr) antihypertensive effect with a rapid onset of action (time to $E_{max}$: 2-4 hr), as well as a 20-fold greater potency than losartan. These results suggest that KR-31125 is a potent, orally active $AT_1$ receptor antagonist that can be applied to the development of new diagnostic and research tools as an added exploratory potential of $AT_1$ receptor antagonist.

Cardiovascular Biofunctional Activity and Antioxidant Activity of Gugija (Lycium chinensis Mill) Species and Its Hybrids (구기자 품종과 교배종의 부위별 심혈관관련 질환 예방 기능성 및 항산화 활성비교)

  • Park, Won-Jong;Lee, Bong-Chun;Lee, Ju-Chan;Lee, Eun-Na;Song, Jung-Eun;Lee, Dae-Hyung;Lee, Jong-Soo
    • Korean Journal of Medicinal Crop Science
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    • v.15 no.6
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    • pp.391-397
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    • 2007
  • To develop new high valuable Gugija (Lycium chinensis), biofunctionalities of Gugija standard species and its hybrids were investigated and compared with each water extracts and methanol extracts from Lycii Fructus, Lycii Folium and buds and Lycii Cortex Radicis. Among various biofunctionalities of Gugija standard species, antioxidant activity was showed the highest in methanol extracts from buds of Cheongwoon species (93%) and antihypertensive angiotensin I-converting enzyme (ACE) inhibitory activity was 84.1% in the water extracts from Lycii Cortex Radicis of Cheongyang NO.7. Futhermore, methanol extracts from Lycii Cortex Radicis of Myungan A-2 hybrid showed 93.1% of antioxidant activity and 96.9% of ACE inhibitory activity was also showed in the methanol extracts from Lycii Fructus of DO148-72(A11) hybrid. However, fibrinolytic activity and anticholesteromia HMG-CoA reductase inhibitory activity were weak or not detected in almost of Gugija standard species and its hybrids. Therefore, we finally selected Cheongwoon Gugija standard species (buds) and Myungan A-2 hybrid (Lycii Cortex Radicis) as good antioxidant sources and also DO148-72 (A11) hybrid (Lycii Fructus) as excellent antihypertensive ACE inhibitior sources for manufacturing functional food product.

Screening of Yeast for Brewing of Korean Traditional Pear Yakju and Optimal Fermentation Condition (전통 배 약주 제조용 효모의 선발 및 배 약주의 최적 발효 조건)

  • Song, Jung-Hwa;Jang, Jeong-Hoon;Na, Kwang-Chul;Kim, Ha-Kun;Lee, Jong-Soo
    • The Korean Journal of Mycology
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    • v.38 no.2
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    • pp.184-188
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    • 2010
  • The goal of this study was to screen a useful yeast for Korean traditional pear Yakju (KTPY) brewing and develop its brewing process. Cooked non-glutinous rice and nuruk were mixed, and added into pear juice with various Saccharomyces cerevisiae and then fermented at $25^{\circ}C$ for 7 days. Among several alcohol fermentation yeasts, ethanol contents was the highest in pear Yakju made by S. cerevisiae K-7 and also showed high ethanol content in pear Yakju which was made by commercial S. cerevisiae C-2. Therefore, we selected S. cerevisiae K-7 and S. cerevisiae C-2 as suitable yeasts for brewing of KTPY. Maximal ethanol production (10.4%) was obtained when cooked non-glutinous rice (100 g) and nuruk (30 sp/g) were mixed and added into pear juice (600 ml) with S. cerevisiae K-7 (5%) and fermented at $25^{\circ}C$ for 7 days and also its antihypertensive angiotensin I-converting enzyme (ACE) inhibitory activity was 57.2%. Addition of antihypertensive starchy materials into the mash was not affected in ACE inhibitory activity and total acceptability of KTPY.

Effect of Raw versus Flavor, Browning and Caking reduced Onion (Allium cepa L.) on Blood Pressure of Spontaneously Hypertensive Rats (향, 갈변 및 케이킹 억제 가공 처리된 양파의 섭취가 SHR 흰쥐의 혈압에 미치는 영향)

  • Choi, Pok-Su;Kwon, Ji-Youn;Han, Myung-Ryun;Han, Myung-Ryun;Kim, Sun-Hee;Chang, Moon-Jeong
    • Journal of the Korean Society of Food Culture
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    • v.23 no.1
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    • pp.55-61
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    • 2008
  • Non processed onion (Allium cepa L.) powder or onion powder processed with ${\beta}-cyclodextrin+1%$ calcium chloride+1% soluble starch solution was added to the diet of 16 week old Wistar and spontaneously hypertensive rats (SHR) for 5 weeks. 36 SHR and Wistar rats were randomly divided into 3 diet groups, each of six. They were named control, NPO (non processed onion), PO (processed onion). The rats of the control group were fed diet without onion powder. To NPO and PO groups were added 5% of non processed onion and processed onion, respectively. Body weight gain, food efficiency ratio (FER), blood pressure, angiotensin converting enzyme (ACE) activity and Na excretion of urine and feces were analyzed. The processed onion and non processed onion diet reduced body weight gain without affeting the total food intake in Wistar rats (p<0.05). The body weight gain was lowest in Wistar rats fed with a diet with processed onion powder. The rats fed with diet containing PO or NPO had lower blood systolic blood pressure in SHR (p<0.05). The effect of onion powder on decreasing the blood pressure was not significant in Wistar rats. The ACE activity in lung was lowered in the SHR fed with either PO or NPO (p<0.05) compared to those fed with control diet. The urinary Na excretion was significantly lower in SHR than Wistar rats. The effects of PO and NPO on increasing the urinary and fecal excretion of Na were significant (p<0.05). These results suggest that onion processed with ${\beta}-cyclodextrin+1%$+1% calcium chloride+1% soluble starch solution to reduce volatile flavor, browning and caking preserves an antihypertensive effect of non processed onion.

Effects of Allicin on the Gene Expression Profile of Mouse Hepatocytes in vivo with DNA Microarray Analysis

  • Park, Ran-Sook
    • Nutritional Sciences
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    • v.8 no.1
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    • pp.23-27
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    • 2005
  • The major garlic component, Allicin [diallylthiosulfinate, or (R, S)-diallyldissulfid-S-oxide] is known for its medicinal effects, such as antihypertensive activity, microbicidal activity, and antitumor activity. Allicin and diallyldisulfide, which is a converted form of allicin, inhibited the cholesterol level in hepatocytes, in vivo and in vitro. The metabolism of allicin reportedly occurs in the microsomes of hepatocytes, predominantly with the contribution of cytochrome P-450. However, little is known about how allicin affects the genes involved in the activity of hepatocytes in vivo. In the present study, we used the short-term intravenous injection of allicin to examine the in vivo genetic profile of hepatocytes. Allicin up-regulate ten genes in the hepatocytes. For example, the interferon regulator 1 (IRF-I), the wingless-related MMTV (mouse mammary tumor virus) integration site 4 (wnt-4), and the fatty acid binding protein 1. However, allicin down-regulated three genes: namely, glutathione S-transferase mu6, a-2-HS glycoprotein, and the corticosteroid binding globulin of hepatocytes. The up-regulated wnt-4, IRF-1, and mannose binding lectin genes can enhance the growth factors, cytokines, transcription activators and repressors that are involved in the immune defense mechanism. These primary data, which were generated with the aid of the Atlas Plastic Mouse 5 K Microarray, help to explain the mechanism which enables allicin to act as a therapeutic agent, to enhance immunity, and to prevent cancer. The data suggest that these benefits of allicin are partly caused by the up-regulated or down-regulated gene profiles of hepatocytes. To evaluate the genetic profile in more detail, we need to use a more extensive mouse genome array.

The Change of Bone Mineral Density by Bisphosphonates Therapy with Calcium-Antagonists in Osteoporosis

  • Kim, Soon-Joo;La, Hyen-Oh;Kang, Young-Sook
    • Biomolecules & Therapeutics
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    • v.16 no.2
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    • pp.141-146
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    • 2008
  • Imbalance in calcium and phosphorous metabolism due to aging or menopause leads to osteoporosis. In contrast to patients with normal blood pressure, hypertensive patients have a higher loss of calcium in the urine with its attendant risk of osteoporosis. The high blood pressure is associated with the risk of bone loss and abnormalities in calcium metabolism leading to calcium loss. So we retrospectively investigated the changes of bone mineral density (BMD) which drugs can have clinical influences over osteoporosis treatments of patients with calcium-antagonists as common antihypertensive drugs and with bisphosphonates which causes a most effective inhibition of osteoclasts resorption. As a result over 70 years of age group and within bisphosphonates group, alendronate 70 mg once-weekly group showed significant increase of BMD in lumbar area. Combination group of cilnidipine and $maxmarvil^{(R)}$ showed very significant decrease of BMD. In conclusion, it is desirable that combination therapy with calcium-antagonists is used carefully in the treatment of osteoporosis with high blood pressure.

Primary aldosteronism with an aldosterone-producing adenoma and contralateral adrenal hyperplasia: A case report (양측성 부신비대와 알도스테론 생성 선종이 동시에 발현된 증례)

  • Park, Hye Won;Lee, Sang Ah
    • Journal of Medicine and Life Science
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    • v.17 no.2
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    • pp.60-63
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    • 2020
  • Primary aldosteronism has been found more often among patients with hypertension. Primary aldosteronism can be caused by an aldosterone-producing adenoma, bilateral adrenal hyperplasia, or rarely by an adrenal carcinoma. An initial diagnostic test for aldosteronism is a measurement of the plasma renin activity and aldosterone concentration. For example, up to 20% of patients with hypertension showed increased plasma aldosterone concentration/renin activity ratio. If surgery is planned, an adrenal vein sampling is necessary for exact localization. Spironolactone, an aldosterone antagonist, is the drug of choice for patients with an aldosterone-producing adenoma or hyperplasia. It can control elevated blood pressure in most primary aldosteronism patients. However, unilateral laparoscopic adrenalectomy is the best treatment for aldosterone-producing adenoma or asymmetrical aldosterone production in patients with uncontrolled hypertension. Here we report a patient with primary aldosteronism caused by unilateral adrenal hyperplasia and a contralateral adrenal adenoma who required as many as five different kinds of antihypertensive medications for controlling elevated blood pressure. The adrenal adenoma was successfully removed by unilateral adrenalectomy and the blood pressure had been controlled well after the surgery.

Effects of Aroma inhalation on Blood Pressure, Pulse Rate, Sleep, Stress, and Anxiety in Patients with Essential Hypertension (아로마 흡입이 본태성고혈압 환자의 혈압, 맥박, 수면, 스트레스, 불안에 미치는 효과)

  • Choi, Eun-Mi;Lee, Kyung-Sook
    • Journal of Korean Biological Nursing Science
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    • v.14 no.1
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    • pp.41-48
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    • 2012
  • Purpose: This experimental research explored the effects of aroma inhalation on blood pressure, pulse, sleep, stress, and anxiety in patients with essential hypertension who are taking antihypertensive medication. Methods: A pilot survey, pre-test and post-test were conducted. The data were collected from August to October, 2009. The participants were 44 patients randomly assigned to an experimental group (22 people) and a control group (22 people). The experimental group received individual instruction for aroma inhalation, which lasted for 3 minutes. They inhaled blended oils of Lavender, Majoram and Ylang Ylang (The mixed ratio was 4:3:3), three times a day, for two weeks. Data from 36 patients were used for the final analysis (20 from the experimental group, 16 from the control group). Data were analyzed using SPSS version 13.0. Results: Sleep disturbance decreased in the experimental group (t=-2.258, $p$=.030). Blood pressure, pulse, stress, and anxiety were not significantly different between the two groups ($p$ >.05). Additional analysis of the experimental group showed that physical stress and psychological stress were significantly lowered. Conclusion: Aroma inhalation is an effective paramedical intervention for patients with essential hypertension.

Simplified HPLC Method for the Determination of Prazosin in Human Plasma and Its Application to Single-dose Pharmacokinetics

  • Gwak, Hye-Sun;Chun, In-Koo
    • Biomolecules & Therapeutics
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    • v.13 no.2
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    • pp.90-94
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    • 2005
  • Prazosin hydrochloride is an antihypertensive drug with selective ${\alpha}_1$-adrenoreceptor blocking effects. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of prazosin in human plasma. A reversed-phase C18 column was used for the separation of prazosin and terazosin (internal standard) with a mobile phase composed of water, acetonitrile and triethylamine(75:25:0.1, V/V;pH5.0) at a flow rate of 1.5 ml/min. the fluorescence detector was set at excitation and emissionwavelengths of 250 and 370 nm, respectively. Intra-and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 0.5 ng/ml. Good recovery (>80%) was seen in plasma. Prazosin was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study in plasma after oral administration of a single 2-mg dose as prazosin base to 16 healthy volunteers. The maximum plasma concentration of prazosin was 23.1 ${\pm}$ 16.5 ng/ml at 2.1 h, and the mean area under the curve and elimination half-life were calculated to be 108.4 ${\pm}$ 74.2 ng ${\cdot}$hr/ml and 2.5 ${\pm}$ 0.6 h, respectively.

Effect of Gamidojeok-san on Hypertension (가미도적산이 고혈압에 미치는 영향)

  • Sin Hwang Su;Oh Young Seon;Kim Yoon Sik;Seol In Chan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1710-1713
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    • 2004
  • This study was Investigated to prove the effect of Gamidojeok-san (Jiaweidaochi-san) on the hypertension. After administer Gamidojeok-san (Jiaweidaochi-san) extract to SHR(Spontaneous Hypertensive Rat) for 5 weeks, we examined changes of blood pressure, pulse rate, aldosterone and catecholamine in serum. Results : Following results were obtained; Gamidojeok-san(Jiaweidaochi-san) showed significant antihypertensive effect. Gamidojeok-san(Jiaweidaochi-san) decreased pulse rate but insignificant. Gamidojeok-san(Jiaweidaochi-san) showed a significant decrease in the aldosterone. Gamidojeok-san(Jiaweidaochi-san) was ineffective on the dopamine. Gamidojeok-san(Jiaweidaochi-san) decreased the norepinephrine but insignificant. Gamidojeok-san(Jiaweidaochi-san) showed a significant decrease in the epinephrine. These results indicate that Gamidojeok-san(Jiaweidaochi-san) can be used in hypertension. Further study will be needed about the functional mechanism and etc..