• Journal of Genetic Medicine
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• 제1권1호
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• pp.17-22
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• 1997

The angiotensin converting enzyme (ACE) is a key component of the renin-angiotensin system thought to be important in the pathogenesis of hypertension and cardiovascular diseases. Deletion polymorphism in the ACE gene may be a risk factor for myocardial infarction. The insertion/deletion (I/D) polymorphism of the ACE detected by PCR analysis appears to be associated with hypertension in Koreans and its nucleotide was subcloned into T-vector and its nucleotide sequences were determined. We also examined an association between hypertension and genetic variance of ACE. We identified the angiotensin I-converting enzyme genotype in 127 hypertensive and 189 normotensive Korean subjects. The distribution of ACE genotype II, ID, DD were 39.2%, 40.2%, 20.6% respectively and the frequency for ACE alleles I and D were 0.593 and 0.407, respectively in all subjects. The frequency of D allele in Korean males is higher than that of Korean females (male; 0.438 : female; 0.267), and the frequency of I allele in Korean females is higher than that of Korean males (female; 0.733 : male; 0.562). Genotype distributions of angiotensin I-converting enzyme genes in Korean normal adult population were different from that of Caucasians (P<0.001). There were no significant differences in genotype frequency between the hypertensive control group (n=127) and the normotensive group (n=189). We observed significant differences of ACE genotype distribution between the male group and the female group in total (P=0.001) and in hypertensive Korean subjects (P=0.013).

• 대한약침학회지
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• 제26권4호
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• pp.298-306
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• 2023

Objectives: Cucumis sativus L. (C. sativus) is vegetable commonly used for managing blood pressure and often consumed in combination with standard antihypertensive therapy, despite lack of scientific evidence supporting their use. Combination of herbs and standard medication could have positive or negative effects. Therefore, this study aimed to evaluate the antihypertensive activity of C. sativus and the combined effect with losartan in the hypertensive rat model induced by angiotensin II. Angiotensin II is a component of the renin-angiotensin-aldosterone system that, upon binding to its receptor, constricts blood vessels leading to elevation of blood pressure. Methods: In an antihypertensive study, rats received C. sativus orally at doses of 9, 18, 27, and 36 mg/kg (full dose); while in a combination study, animals received losartan 2.25 mg/kg combined by either with C. sativus 9 or 18 mg/kg. The standards group received losartan 2.25 mg/kg or 4.5 mg/kg (full dose). Results: Blood pressure was measured using the tail-cuff method. C. sativus significantly attenuated angiotensin II-induced hypertension as observed in groups receiving C. sativus at 9, 18, 27, and 36 mg/kg at 30 minutes after induction showed the average change (Δ) of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with respect to time zero were 28.8/18.3, 24.8/15.8, 22.8/15.5, and 11.5/9.0 mmHg, respectively. Whereas the average change (Δ) of SBP and DBP in the rats receiving the combination of half doses of C. sativus and losartan were 8.8/9.0 mmHg, respectively. These diminished effects were better than a full dose of C. sativus and comparable with a full dose of losartan (6.5/7.8 mmHg). Conclusion: The present findings indicate that C. sativus dose-dependently blocks blood pressure elevation induced by angiotensin II. The combination of half dose of C. sativus and losartan has an additive effect in lowering blood pressure.

• 대한임상검사과학회지
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• 제43권2호
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• pp.43-47
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• 2011

Angiotensin converting enzyme (ACE) is a vital enzyme in the renin-angiotensin-aldosterone system, and there are literature reports describing its relationship between the ACE polymorphism and muscular strength, muscular endurance and flexibility. The purpose of this study is to identify the distribution of the ACE gene polymorphism among individual golfers and the relationship between different golfers group. We analyzed the ACE gene polymorphism to study the individual differences among professional golfers (n=35), junior golfers (n=30) and general golfers (n=25). Genotype frequencies of DD, ID and II in total golfers (n=90) were 16.7%, 52.2% and 31.1% respectively. In professional golfers, the frequencies of DD, ID and II were 25.7%, 45.7% and 28.6% respectively. The frequency of DD genotype in professional golfers was higher than in junior golfers and in general golfers, but the II genotype in professional golfers was lower than in other groups. In conclusion, these data suggest that the capability and power of golf exercise are associated with the hereditary characteristics of the ACE polymorphism.

• 한국식품과학회지
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• 제46권3호
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• pp.375-383
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• 2014

본 연구는 복분자 완숙과 50% 에탄올 추출물을 이용하여 인간제대정맥내피세포주(HUVEC)에서 복분자 추출물이 NO의 생성에 미치는 영향과 ACE 단백질 발현을 조사하였으며, 본태성 고혈압 흰쥐(SHR)에서 혈압강하 효과 및 혈압의 조절과 관련 깊은 인자들(renin, AT1-R, ET-1, IL-6)의 유전자 발현 그리고 혈관조직의 변화를 조사하였다. 그 결과 복분자 완숙과 50% 에탄올 추출물은 HUVEC 세포주에서 NO의 생성을 촉진하였으며 혈관수축활성을 가지는 ACE 단백질의 발현을 억제하였고 본태성 고혈압 흰쥐에게 복분자 완숙과 에탄올 50% 추출물을 8주간 투여한 결과 혈액 내 ACE의 활성이 억제되었으며 renin 및 혈관 수축인자인 ET-1 유전자의 발현이 억제되고 염증관련 유전자인 IL-6의 발현이 억제됨을 확인하였다. 그리고 신세동맥의 두께 및 심근 호산성세포수를 감소시켜 혈관내피세포의 손상을 보호하며 심장의 병변을 경감시키는 효과가 있음을 확인하였다. 본 연구 결과 복분자 완숙과 추출물은 혈압 조절과 연관된 단백질 및 유전자의 발현과 활성을 조절하고, 혈관의 두께 및 심근의 변성을 감소시켜 혈압 강하에 도움이 되는 것으로 나타났으며 향후 심혈관계 질환을 개선시킬 수 있는 식품소재로서의 가능성이 있음을 확인하였다.

• Childhood Kidney Diseases
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• 제7권1호
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• pp.52-59
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• 2003

목적 : 레닌-안지오텐신계는 신장의 성장과 발달에 중요한 역할을 하는 것으로 알려져 있으며, 안지오텐신 II는 신장형성기 동안 중요한 역할을 담당한다. 저자들은 터너 증후군 환자에서 신기형의 발생빈도를 조사하고, 신기형이 동반된 군과 동반되지 않은 군으로 분류하여 양군 사이에 레닌-안지오텐신계 유전자의 분포에 차이가 있는지를 조사하였다. 방법 : 말초혈액의 임파구를 사용하여 세포분 석학적 방법으로 진단된 33명의 터너 증후군 환자를 대상으로 신요로계의 기형여부를 초음파검사와 경정맥 요로 조영 검사, DMSA scan으로 진단하고, 더불어 안지오텐신전환효소의 유전자형, 안지오텐시노겐 유전자형, 안지오텐신 수용체유전자형의 분포를 핵산증폭법을 사용해 조사하였다. 결과 : 33명의 터너 증후군 환자 중 12명에서 신기형이 동반되어 전체적으로 36.4%의 빈도를 나타내었다. 핵형에 따른 신기형의 빈도를 살펴보면 전형적인 45,X형의 경우는 18명 중 8명에서 관찰되어 44.4%의 빈도를 나타내었고, 모자이시즘과 X 염색체구조상의 이상인 경우에는 15명 중 4명에서 관찰되어 26.7%의 빈도를 나타내어, 전형적인 45,X형의 경우에서 발생빈도가 높았으나 통계적으로 유의하지는 않았다(P>0.05). ACE 유전자형의 분포는 신기형 동반군에서 DD형이 0%, ID형이 73%, 그리고 II형이 27%이었으며, 신기형이 동반되지 않은 군에서는 DD형이 11%, ID형이 56%, II형이 33%로 양군 사이에는 ACE 유전자형의 분포는 유의한 차이가 없었다. AGT M235T 유전자형의 분포는 신기형 동반군에서 MM형이 82%, MT형이 8%, 그리고 TT형이 0%이었으며, 신기형이 동반되지 않은 군에서는 MM형이 56%, MT형이 33%, TT형이 11%로 양군 사이에는 AGT M235T 유전자형의 분포는 유의한 차이가 없었다. ATR 1 유전자형의 분포는 신기형 동반군에서 AA형이 91%, AC형이 9%, 그리고 CC형이 0%이었으며, 신기형이 동반되지 않은 군에서는 AA형이 94%, AC형이 6%, CC형이 0%로 양군 사이에는 ATR 1 유전자형의 분포도 유의한 차이가 없었다. 결론 : 터너증후군 환자에서 신기형의 동반율은 36.4%였으며, 45,X형에서 발생빈도가 높았으나 통계적으로 유의하지는 않았다. 신기형이 동반된 군과 동반되지 않은 군 사이에는 레닌-안지오텐신계 유전자의 분포는 모두 유의한 차이가 관찰되지 알았다.

• Childhood Kidney Diseases
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• 제4권2호
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• pp.127-135
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• 2000

목 적 : Cyclosporine(CsA)는 면역 억제제로서 중요한 역할을 하고 있지만 가장 중요한 부작용인 신독성 때문에 사용에 제한이 있다. 이에 저염식이를 한 쥐에서 유발되는 만성 CsA 신증에서 angiotensin converting enzyme 억제제(ACEI)가 미치는 영향을 검색하고자 하였다. 대상 및 방법 : 흰 쥐를 대상으로 하여 표준식이(NSD), 저염식이(LSD), NSD+CsA. LSD+CsA, NSD+CsA+ACEI, LSD+CsA+ACEI를 1-6군으로 분류하여 공급하였다. 6주 후 혈중 CsA농도, 혈청 sodium, potassium, GFR을 측정하였고, 신장의 조직검사를 시행하였다. 성 적 : 혈중 CsA농도와 sodium치는 각 군간에 차이가 없었고 potassium치는 CsA 단독 투여시에는 식이군간에 차이가 없었으나, CsA와 ACEI를 병용 투여시에는 NSD군에 비해서 LSD군에서 유의하게 증가하였다. (P<0.05). 사구체 여과율은 CsA만 투여한 경우나 CsA와 ACEI를 병용투여한 경우에서 NSD군에 비해 LSD군에서 유의하게 감소하였고 NSD를 시행한 경우에서는 CsA만 투여한 경우보다 ACEI를 병용투여했을 때 GFR이 더 감소하였다 (P<0.05). 조직학적 소견은 CsA투여에 의한 근위부 세뇨관 위축, 간질의 섬유화와 PAS염색 양성인 과립들이 출현하였고 이는 NSD군보다 LSD군에서 더 저명하였으며 ACEI를 병용시에도 LSD군에서 이러한 변화가 더 저명하게 관찰되었으나 ACEI 투여 전과는 큰 차이를 보이지 않았다. 결 론 : 본 연구에서는 염분 부족은 renin-angiotensin system을 활성화해서 CsA 신증을 더욱 가중시키며, ACEI는 LSD로 유발된 CsA 신증에서 신기능의 화학적 지표와 조직학적으로 더욱 악화시컸다. 이 결과로 LSD로 인해 더욱 조장될 수 있는 간접적인 신허혈 상태에서는 ACEI는 신관류를 개선하지 못하고, 이로 인해 신독성이 더욱 악화될 수 있을 것으로 생각되었다.

• Journal of Preventive Medicine and Public Health
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• 제53권6호
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• pp.476-486
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• 2020

Objectives: The objective of this study was to estimate the risk of lung cancer in relation to angiotensin II receptor blocker (ARB) use among patients with hypertension from the Korean National Health Insurance Service-National Health Screening Cohort. Methods: We conducted a retrospective cohort study of patients with hypertension who started to take antihypertensive medications and had a treatment period of at least 6 months. We calculated the weighted hazard ratios (HRs) and their 95% confidence intervals (CIs) of lung cancer associated with ARB use compared with calcium channel blocker (CCB) use using inverse probability treatment weighting. Results: Among a total of 60 469 subjects with a median follow-up time of 7.8 years, 476 cases of lung cancer were identified. ARB use had a protective effect on lung cancer compared with CCB use (HR, 0.75; 95% CI, 0.59 to 0.96). Consistent findings were found in analyses considering patients who changed or discontinued their medication (HR, 0.50; 95% CI, 0.32 to 0.77), as well as for women (HR, 0.56; 95% CI, 0.34 to 0.93), patients without chronic obstructive pulmonary disease (HR, 0.75; 95% CI, 0.56 to 1.00), never-smokers (HR, 0.64; 95% CI, 0.42 to 0.99), and non-drinkers (HR, 0.69; 95% CI, 0.49 to 0.97). In analyses with different comparison antihypertensive medications, the overall protective effects of ARBs on lung cancer risk remained consistent. Conclusions: The results of the present study suggest that ARBs could decrease the risk of lung cancer. More evidence is needed to establish the causal effect of ARBs on the incidence of lung cancer.

• 대한약침학회지
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• 제22권2호
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• pp.95-101
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• 2019

Objectives: Angiotensin II (AngII), a major product of renin-angiotensin system (RAS) has important role in induction of hypertension and antihypertensive effect of several medicinal plant was mediated by effect on this agent. Therefore, this study examined the possible effect of hydroalcoholic extract of Crocus sativus (C. sativus) on hypertension induced by AngII. Methods: Six groups (n = 6) of rats were used as follow: 1) Control, 2) AngII (300 ng/kg), 3) Losartan (Los, 10 mg/kg) + AngII and 4-6) C. sativus extract (10, 20 & 40 mg/kg,) + AngII. The femoral artery and vein were cannulated for recording cardiovascular parameters and drugs administration, respectively. All drugs were injected intravenously (i.v). Los and all doses of C. sativus injected 10 min before AngII. Systolic blood pressure (SBP), mean arterial blood pressure (MAP) and heart rate (HR) were recorded throughout the experiment and those peak changes (${\Delta}$) were calculated and compared to control and AngII. Results: AngII significantly increased ${\Delta}MAP$, ${\Delta}SBP$ and ${\Delta}HR$ than control (P < 0. 01 to P < 0.001) and these increments were significantly attenuated by Los. All doses of C. sativus significantly reduced peak ${\Delta}MAP$, ${\Delta}SBP$, and ${\Delta}HR$ than AngII group (P < 0. 05 to P < 0.001). In addition, peak ${\Delta}MAP$, ${\Delta}SBP$ in doses 10 and 20 were significant than Los + AngII group (P<0.05 to P< 0.01) but in dose 40 only MAP was significant (P<0.05). Peak ${\Delta}HR$ in all doses of C sativus was not significant than Los+ AngII. Conclusion: Regarding the improving effect of the C. sativus extract on AngII induced hypertension, it seems that this ameliorating effect partly mediated through inhibition of RAS.

• Environmental Analysis Health and Toxicology
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• 제20권4호통권51호
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• pp.303-309
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• 2005

Essential hypertension has been considered as multifactorial disease resulted from the interaction of both environmental and genetic factors. The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure homeostasis. Recently, a homologue of angiotensin I converting enzyme, ACE2 has been focused on as a candidate gene of essential hypertension in the experiments using animal model and human being. In this study, we carried out an association study in order to clarify the relationship between the A 1075G polymorphism in the ACE2 gene and essential hypertension in Korean subjects. Because this polymorphism is located on human chromosome X, the statistical analysis for each gender was performed separately. There were no significant differences in allele distribution of the A 1075G polymorphism in the ACE2 gene between normotensives and hypertensives in the both gender groups, respectively. However, this polymorphism was significantly associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) values in only female groups (P< 0.05). Thus, these results may suggest the probable role of ACE2 gene in the inter-individual susceptibility of female group to blood pressure variability.

• 약학회지
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• 제43권6호
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• pp.843-850
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• 1999

We investigated whether endothelium-derived NO and endothelin-1 might result enhanced vasoconstriction induced by administration of norepinephrien (NE) at the early stage of one-kidney, one-clip (1K1C) renal hypertensive rats. We also studied the relation ship of renin-angiotensin system (RAS) using rat aorta in this hypothesis. L-NMMA (30$\mu$M) and L-NAME(30${\mu}M$) enhanced vasoconstriction induced by NE in thoracic aorta of control rats. However angiotensin converting enzyme (ACE) inhibitor didn't. The aorta of 1KIC rats showed a singnificantly exaggerated contractile response to NE as compared with control rats. Rub-bing the endothelium abolished this difference. Ach and SNP-induced vasorelaxation show no significant difference between 1KIC and control rats. The treatment of phosphoramidon (10${\mu}M$) and oral administration of captopril (0.05, w/v%) abolished the exaggerated contractile response to NE at early stage of 1KIC rats. These results suggest that the increase of contractile response at the early phase in 1KIC rat is partially involved in the activation of ACE.