• Title/Summary/Keyword: Renin

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The Effect of Angiotensin Converting Enzyme Inhibitor on Chronic Cyclosporine Nephropathy in Salt Depleted Rats (저염식이를 이용한 cyclosporine 신독성에서 angiotensin converting enzyme Inhibitor의 영향)

  • Lee Eun-Ju;Lee Eun-Sil;Hah Jung-Hi;Kim Yong-Jin;Park Yong-Hoon
    • Childhood Kidney Diseases
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    • v.4 no.2
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    • pp.127-135
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    • 2000
  • Purpose: Cyclosporine(CsA) is a potent immunosuppressant but the use of CsA is associated with various side effects, especially nephrotoxicity. In tile kidney, salt depletion activates tile renin-angiotensin-aldosteron(RAS) system and accentuates chronic CsA nephropathy. We postulate that angiotensin converting enzyme inhibitors(ACEI) can prevent chronic CsA nephropathy, since ACEI may inhibit this cascades. This study was aimed to assess the effect of ACEI on chronic cyclosporin nephropathy in salt depleted rats. Methods: 36 Fischer-344 rats were divided into 6 goups. Group I received normal salt diet(NSD). Group II received a low salt diet(LSD). Group III received CsA with a NSD. Group IV received CsA with a LSD. Group V received NSD+CsA with ACEI. Group VI received LSD+CsA with ACEI. Rats were sacrificed after six weeks and the glomerular filtration rate(GFR), serum sodium, potassium and whole blood cyclosporine levels were measured. Renal tissues me sampled for the observation of histological changes. Results: No differences in blood CsA level & serum sodium were found between groups during the course of this experiment. Serum potassium in group VI was significantly increased compared with group IV and V (P<0.05). In groups treated with CsA only and in those where CsA was combined with ACEI, GFR was found to be significantly more decreased in LSD than NSD, and GFR in group V was significantly decreased in comparison with group III (P<0.05). Renal histologic lesions associated with CsA which consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles were more severe in tile LSD group. But, no differences were observed between tile groups treated with CsA and ACEI, and the groups treated with only CsA. Conclusion: Salt depletion associated with the activation of the RAS system accentuated chronic CsA nephrotoxicity, but, ACEI could not reduce the functional and morphological changes of salt depleted kidneys, in which nephropathy can be exacerbated in spite of the blocking of the angiotensin II pathway. further studies are required to elucidate whether Am ameliorated the effect of salt-depleted CsA nephrotoxicity upon the effective renal blood flow.

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A Experimental Study on the Effect of Hwangryeonheadock-Tang and Onchung-Eum on Hyperlipidemia & Hypertension (황연해독탕(黃連解毒湯)과 온청음(溫淸飮)이 고혈압(高血壓) 및 고지혈증(高脂血症)에 미치는 영향(影響))

  • Kim, Eun-Sun;Park, Chi-Sang;Park, Chang-Gook
    • The Journal of Korean Medicine
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    • v.20 no.1 s.37
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    • pp.185-196
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    • 1999
  • The aim of the present study was to investigate the effect of Hwangryeonheadock-Tang and Onchung-Eum on essential hypertension and hyperlipidemia. Rats were orally administered for 30days with Hwangryeonheadock-Tang and Onchung-Eum and the blood was withdrawn at 10, 20 and 30days after an oral administration. The heart rate, tail blood pressure, plasma renin activity, plasma level of aldosterone. catecholamine, sodium and angiotensin II were measured after an oral administration of Hwangryeonheadock-Tang and Onchung-Eum in spontaneously hypertensive rat(SHR). In addition, serum levels of total cholesterol, triglyceride, HDL-cholesterol. LDL-cholesterol and total lipid were measured cholesterol-fed rats. The results were summarized as follows ; 1. A significant decrease of tail blood pressure was shown at 10, 20 and 30days after Hwangryeonheadock-Tang and Onchung-Eum treatment in SHRs. compared with saline. 2. Heart rate was significantly decreased at 30days in SHRs after Hwangryeonheadock-Tang treatment and at 20, 30days after Onchung-Eum treatment in SHRs. compared with the effects of saline group. 3, A significant decrease of plasma aldosterone level was elicited at 10, 20days after Hwangryeonheadock-Tang treatment in SHRs, compared with the effects of saline group, 4. Plasma renin activity was significantly decreased at 10days after Onchung-Eum treatment compared with the effects of saline group in SHRs. 5. Plasma norepinephrine level was significantly decreased at 20 and 30clays after Onchung-Eum treatment in SHRs, compared with the effects of saline group. 6. A significant decrease of plasma epinephrine level was induced at 30days after Hwangryeonheadock-Tang treatment and at 10, 20 and 30days after Onchung-Eum treatment, compared with the effects of saline group in SHRs. 7. Plasma sodium level was. significantly decreased at 20days after Hwangryeonheadock-Tang and Onchung-Eum treatment, compared with the effects of saline group in SHRs. 8. Plasma angiotensin II level was significantly decreased at 30days after Onchung-Eum treatment, compared with the effects of saline group in SHRs. 9. A significant decrease of body weight was observed at 20 and 30days after Hwangryeonheadock-Tang treatment and at 10, 20 and 30days after Onchung-Eum treatment. compared with the effects of saline group in hyperlipidemia rats. 10. Hwangryeonheadock-Tang and Onchung-Eum showed a significantly decreasing effect at 30days on serum total cholesterol level in hyperlipidemia rats, compared with the saline treatment. 11. Hwangryeonheadock-Tang and Onchung-Eum saw 20 and 30days respectively on serum triglyceride level in the saline treatment. 12. Hwangryeonheadock-Tang and Onchung-Eum decreased on serum HDL-cholesterol level significantly, compared with the saline treatment in hyperlipidemia rats. 13. A significant decrease of serum LDL-cholesterol was observed at 10 and 30days after Hwangryeonheadock-Tang treatment and at 30days after Onchung-Eum treatment, compared with the effects of saline group in hyperlipidemia rats. 14. Hwangryeonheadock-Tang had a significantly decreasing effect at 10, 20 and 30days on serum total lipid level, compared with the saline treatment in hyperlipidemia rats. 15. Hwangryeonheadock-Tang elicited a significantly decreasing effect on weight of kidneys, spleen and testes respectively and Onchung-Eum induced on weight of liver and spleen respectively in hyperlipidemia rats, compared with saline treatment. These Findings suggest a possible anti-hypertensive and anti-hyperlipidemic effect of Hwangryeonheadock-Tang and Onchung-Eum.

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Acute and Chronic Effects of Ethanol on the Cardiovascular and Hormonal Responses to Hemorrhage in Conscious Normotensive and Spontaneously Hypertensive Rats

  • Park, Yoon-Yub;Lee, Joong-Hee;Park, Jae-Sik;Yang, Eun-Kyoung;Ahn, Dong-Kuk;Kim, Hyeong-Jin;Lee, Won-Jung
    • The Korean Journal of Physiology
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    • v.27 no.1
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    • pp.67-77
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    • 1993
  • Acute and chronic effects of ethanol (EOH) administration on the cardiovascular and hormonal responses to repeated hemorrhage were investigated in conscious normotensive Wistar rats and spontaneously hypertensive rats (SHR). The chronic EOH treated group received 5% EOH (vol/vol) ad libitum in the drinking water far the first week,10% for the last 2 weeks, and 20% for the last 5 weeks from the age of 6 weeks. The EOH free group received tap water. Chronic EOH and EOH free groups were randomly subdivided into acute EOH infusion and control groups. Under ether anesthesia, catheters were inserted into the femoral vein and both femoral arteries. After rats regained consciousness and their blood pressure was stabilized, responses to quick hemorrhage (5 ml/kg BW) were tested. In the acute EOH infusion group, hemorrhage was induced 20 min after EOH infusion (1.0 g/kg BW), Baroreceptor reflex sensitivity was assessed by the ratio of changes in hen.1 rate and mean arterial pressure (${\Delta}HR/{\Delta}MAP$) immediately after the hemorrhage. Chronic EOH administration elevated MAP in Wistar rats. During acute EOH infusion, MAP do- creased and HR increased in all groups. In comparison to EOH free control rats, acute or chronic EOH treated rats showed a greater reduction in MAP and a smaller elevation in heart rate in response to a hemorrhage. The degree of MAP reduction was significantly greater in SHR than in Wistar rats. Both the acute and chronic EOH administration attenuated the baroreceptor reflex and retarded MAP recovery, again the trend being much more prominent in SHR. The increase in plasma vasopressin and lenin concentrations after hemorrhage were intensified by the chronic EOH administration. SHR showed a greater vasopressin response but a smaller lenin response than Wistar rats. These results indicate that the EOH treated rats, particularly SHB, are prone to shock by a hemorrhage, which may be partly attributed to an impaired baroreceptor reflex function.

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An Intravenous Replenishment of Salivary Components and Dry Forage Intake in Freely Drinking Large-type Goats

  • Sunagawa, K.;Hashimoto, T.;Izuno, M.;Hashizume, N.;Okano, M.;Nagamine, I.;Hirata, T.
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.4
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    • pp.538-546
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    • 2008
  • Large-type goats eating dry forage secreted large volumes of saliva which resulted in the loss of $NaHCO_3$ from the blood and decreased plasma volume (hypovolemia). This research investigated whether or not the loss of $NaHCO_3$ from the blood and hypovolemia brought about by dry forage feeding actually depresses feed intake in large-type goats under free drinking conditions. The present experiment consisted of three treatments (NI, ASI, MI). All treatments in this experiment were carried out under free drinking conditions. In the NI control (NI), a solution was not infused. In the ASI treatment, i.v. infusion of artificial saliva was initiated 2 h before feeding and was continued for a total of 3 h concluding 1 h after the commencement of the feeding perod. In the MI treatment, mannitol solution was infused to replenish only water lost from the blood in the form of saliva. The hematocrit and plasma total protein concentrations during feeding in the NI control were observed to be higher than pre-feeding levels. This indicated that dry forage feeding-induced hypovolemia was caused by the accelerated secretion of saliva during the initial stages of feeding in freely drinking large-type goats. Increases in hematocrit and plasma total protein concentrations due to dry forage feeding were significantly suppressed by the ASI treatment. While hematocrit during feeding in the MI treatment was significantly lower than the NI control, plasma total protein concentrations were not different. From these results, it is clear that the MI treatment was less effective than the ASI treatment in mitigating the decreases in plasma volume brought about by dry forage feeding. This indicates that plasma volume increased during dry forage feeding in the ASI treatment which inhibited production of angiotensin II in the blood. The ASI treatment lessened the levels of suppression on dry forage feeding, but the MI treatment had no effect on it under free drinking conditions. The results indicate that despite the free drinking conditions, increases in saliva secretion during the initial stages of dry forage feeding in large-type goats caused $NaHCO_3$ to be lost from the blood into the rumen which in turn caused a decrease in circulating plasma volume and resulted in activation of the renin-angiotensin system and thus feeding was suppressed.

The Preventive Effect of Captopril on VEGF Expression in Streptozotocin-induced Diabetic Retiniopathy (당뇨병성 망막증에 있어서 Captopril에 의한 VEGF 발현 저하 효과)

  • Bae, Chun-Sik;Lim, Seul-Ki;Park, Min-Jung;Han, Ho-Jae;Kim, Kye-Yeop;Jeong, Soo-Young;Yoon, Kyung-Chul;Park, Soo-Hyun
    • Applied Microscopy
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    • v.39 no.2
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    • pp.81-87
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    • 2009
  • Diabetic retinopathy is one of major complications of diabetes mellitus, which is associated with the dysfunction of retina. It has been reported that the onset of diabetic retinopathy is related to the activation of renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE), which converts angiotensin I into angiotensin II, is a key component of RAS. Among many growth factors, vascualr endothelial growth factor (VEGF) is an important cytokine in the neovasculization of retina, which is a characteristics of diabetic retinopathy. However, the relationship between ACE and VEGF was not elucidated in diabetic retinopathy. Thus, this study was conducted to examine the protective effect of captopril, an ACE inhibitor, in the retina of streptozotocin (STZ)-treated diabetic rats. In present study, STZ-treated diabetic rats exhibited the increase of VEGF levels in serum and retina. The serum levels of VEGF in STZ-treated diabetic rats was not blocked by the treatment of captopril. However, the retina levels of VEGF in STZ-treated diabetic rats was blocked by the treatment of captopril, suggesting the local action of captopril in retina. Immunohistochemical analysis also revealed that the retina of STZ-treated diabetic rats manifested the increase of ganglion cell layers, outer nuclear layers, and inner nuclear layers, which were also prevented by the treatment of captopril. In conclusion, captopril prevented the expression of VEGF in the retina of STZ-treated diabetic rats.

Studies on Manufacturing of Gouda Type Cheese by using of Crystalline Mucor Rennin (Crystalline Mucor Rennin을 이용한 치즈제조에 관한 연구)

  • Yu, Ju-Hyun;Kim, Yu-Sam;Hong, Yun-Myung
    • Korean Journal of Food Science and Technology
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    • v.3 no.1
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    • pp.6-14
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    • 1971
  • Crystalline Mucor rennin and Mucor rennet from Mucor pusillus var. Lindt was compared with Hansen's calf rennet in its properties as a milk clotting enzyme. The method of Gouda type cheese from domestic milk was established by using of Crystalline Mucor rennin and Mucor rennet. The cheese produced by using of Mucor rennet as a milk clotting enzyme sometimes had bitter taste, it can be reduced with using Crystalline Mucor rennin, instead of Mucor rennet. It was also found out that these cheeses could be colored by the pigment from Cape Jasmine which is wildly ubiquitous in Korea.

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An Experimental Study of Effect on ECV 304 Cells, Platelet Rich Plasma and Rats treated with L-NAME by Ondamtang extract (온담탕이 고혈압 백서와 인간유래 혈관내피세포주(ECV 304)에 미치는 영향)

  • Baek Il-Sung;Park Chang-Gook;Lee So-Yeon;Yoon Hyeon-Deok;Sin Wo-Chul;Park Chi-Sang
    • Herbal Formula Science
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    • v.12 no.2
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    • pp.175-202
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    • 2004
  • Nitric oxide(NO) play an important role in normal and pathophysiological cells including as a messenger molecule, neurotransmitter, microbiocidal agent, or dilator of blood vessels and artheriosclerosis, hypertension, myocardial infarction, respectively. To investigate that Ondamtang in the potential contribution of the levels of nitric oxide generated by endothelial nitric oxide synthase (eNOS) and the mechanisms of protection against L-NAME, human ECV304 cells, which normally do not express eNOS, were expressed by L-NAME. L-NAME stimulated rat or cells were found to be resistant to injury and delayed death following the Ondam-tang. Inhibition of nitric oxide synthesis abolished the protective effect against L-NAME, thrombin and collagen exposure. Interestingly, such effects have bee observed during stimulation with agents such as KCl on L-NAME mediate rats, were damaged by the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Cardiovascular diseases is one of the blood vessels and renin-angiotensin system dynfunction. So we studied on herbal medicine that have a relation of vessels endothelium necrosis. In Oriental Medicine, Ondam-tang has been used for disease in relation to cardiovascular system. We studied on the protection and inhibitory effects of cardiovascular diseases in L-NAME induced rat or ECV304 cell lines through the Cell morphological pattern, Tunel assay, LDH activity, heart rate, blood pressure and immunohistochemistric analysis by Ondam-tang. As the result of this study, In group, the anti-apoptosis and necrosis in the cardiovascular system have a potential capacity for prevented, protected and treating the diseases of cardiovascular system, against the necrosis of rat and ECV304 cells with eNOS and calpain expression by L-NAME is promoted.

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The Effect of Dodamtang(DDT) on Brain damage and Hypertension (도담탕(導痰湯)이 뇌손상(腦損傷) 및 고혈압(高血壓)에 미치는 영향(影響))

  • Lim, Seong-Min;An, Joung-Jo;Choi, Young;Kim, Yong-Jin;Yoo, Ho-Ryoung;Park, Yang-Chun;Seol, In-Chan;Hwang, Chi-Won;Cho, Hyun-Kyung
    • The Journal of Internal Korean Medicine
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    • v.22 no.4
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    • pp.503-512
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    • 2001
  • Objective : This study was carried out to investigate the effects of DDT on the brain damage and hypertension. Methods : We observed the effect of Dodamtang(DDT) extract on KCN-induced coma, focal brain ischemia by MCA occlusion, cytotoxicity and protection of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35). To prove the effect of DDT as a blood pressure depressant, we measured aldosterone, renin activity, catecholamine, sodium and NO density using the seperated blood plasma. Results : DDT showed a protective effect on cytotoxicity of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35) in a dose dependent manner and proved the significant abridgement of brain ischemic area and edema induced by MCA occlusion, a critical decrease of neurologic deficitic grade in the fore-limbs. DDT didn't reduce the duration of KCN(1.87mg/kg iv.)-induced coma and prolonged the survival rate in the case of KCN(3.0mg/kg iv.)-induced coma by the ratio of 20%. While DDT increased the value of NO in SHR, it significantly decreased the blood pressure of SHR and the value of aldosterone& epinephrine in SHR. Conclusions : These results suggested that DDT might be usefully applied for treatment of hypertension, cerebral infarction, and brain damage.

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The Comparative Effects of Yugmijihwangtang in Donguibogam and Experiment Research Results -Focusing on the Korean Medicine and Traditional Chinese Medicine- (육미지황탕 효능의 동의보감과 실험연구결과의 비교고찰 -한의학과 중의학을 중심으로-)

  • Han, Yoochang;Kim, Myung Dong;Lee, Sundong
    • Herbal Formula Science
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    • v.25 no.2
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    • pp.223-251
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    • 2017
  • Objectives : A lot of experiment results of Yugmijihwangtang(YM) are reported in various kinds of journals. Many of them report on the new effects that are not recorded in the traditional medical texts. So it is necessary to take it into consideration that newly reported effects could be of help to clinical practice, because this process of comparison of Donguibogam and scientific experiment results will have basis to lead into the evidence based medicine. Methods : We compared the effects of in Donguibogam and the experiment results of YM. Results : The effects of YM in Donguibogam are to replenish essence and marrow, and to treat red wen, fatigue, treat hypouresis, urinary sediment, urinary urgency, hematuria, hydrocephalus, speech and movement retardation, yin-deficiency, diabetes mellitus, nonalcoholic fatty liver, melanoma, disability to see near and far sight, tinnitus, hearing loss, alopecia, angiogenesis, cough, cough at night, trachyphonia, and, infantile convulsion. The experiment results of YM since 2000 in both Korea and China are to inhibit atopic dermatitis, renal interstitial fibrosis, anti-oxidant, emphysema, stress, glomerulosclerosis, diabetic nephropathy, chronic glomerulonephritis, hemorrhage, plantar sweating, dermal aging, kidney aging, bone loss, breast cancer, pathological myocardial cell, primary liver cancer, thrombosis, osteoporosis, intrauterine growth retardation, chronic renal failure, IgA nepropathy, slow cerebral development, and hippocampal tissue lesions on the one hand, and to help bone formation, renin-angiotensin- aldosterone system, cerebral recovery, cognitive function and expression, osteoblast proliferation and differentiation, learning and memory, cold-tolerance and oxygen deficit-tolerance and anti-fatigue, endometrial formation, humoral and cell-mediated immunity, immune regulation effect, Hypothalamus-Pituitary-Ovary Axis, and spermatogenesis, on the other hand. Conclusion : When we compared the effects of YM with the experiment results of YM, there existed a considerable gap between them. So, from now on, it is expected that a great effort and consideration are needed to solve these gaps from an academic and clinical point of view.

The Evaluation of Potential Hepatotoxicity by Calcium Channel Blockers, Renin-Angiotensin System Blockade and Diuretics (칼슘채널차단제, 레닌-안지오텐신시스템 차단제, 이뇨제의 잠재적 간독성 평가)

  • Kim, Jae Yun;Lee, Ok Sang;Jung, Sun Hoi;Lee, Hye-Suk;Lee, Chang Ho;Kim, Sang Geon;Lim, Sung Cil
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.4
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    • pp.330-339
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    • 2012
  • Background : Hypertension is treated with both lifestyle modification and pharmacotherapy. The Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), published in 2003, provides a streamlined management approach to hypertension for the primary care physician. The JNC-7 is the gold standard also in Korea. According to the JNC-7, special therapeutic considerations are recommended for high-risk individuals with compelling indications. The presence of compelling indications in any given patient should be considered when selecting specific pharmacotherapy to treat hypertension. However, in patients with compelling indications, it is unknown that hepatotoxicity is caused by Calcium Channel Blocker (CCB), one of 1st anti-hypertensive drugs. Now, the CCB is the most used 1st anti-hypertensive drug in Korea Therefore, we evaluated the changes in blood liver function parameters (ALT, AST, Total bilirubin, serum albumin) for the study group. Methods : We randomly collected and retrospectively analyzed Electronic Medical Record data (n=28,788) of patients, and who took calcium channel blockers(non-dihydropyridines; diltiazem, verapamil, dihydropyridines; amlodipine, barnidipine, benidipine, clinidipine, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine), with having liver function tests (LFTs) from July 1st 2009 to June 30th 2010 at the Seoul National University Hospital in Korea. Control groups are two antihypertensive agents: RAS blockade (ARB; candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, ACE-I; cilazapril, enalapril, fosinopril, imidapril, perindopril, ramipril) and, Diuretics (loop; furosemide, torsemide, thiazide; hydrochlorothiazide[HCTZ], indapamide). Patients not having LFT results at these three standard points of time(baseline, during, medication, and after finishing medication) were excluded. The collected data were analyzed by using the SPSS (Version12.0) and Microsoft Excel (Version2007). Results : 711 patients who were treated CCB (297), RAS blockade (232) or Diuretics (182) monotherapy were selected for the study. In selected patients, liver damage degree(changes of each LFTs value) was higher in diuretics group than other groups, followed by RAS blockade and CCB. In diuretics group's was loop-diuretics group was higher than thiazide-diuretics group. In CCB group, Nondihydropyridine-CCB's damage degree was higher than Dihydropyrine-CCB's that. Conclusions : Despite the limitations due to the retrospective study, among patients with abnormal LFTs, the use of CCBs led to a less liver damage than other 1st anti-hypertensive agents. It can be recommended CCBs as one of the initial treatments of hypertension in patients with liver disease.