• Childhood Kidney Diseases
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• v.28 no.2
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• pp.51-58
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• 2024

Patients with chronic kidney disease (CKD) bear a significant financial burden and face numerous complications and higher mortality rates. The progression of CKD is associated with glomerular injury caused by glomerular hyperfiltration and oxidative stress. Factors such as uncontrolled hypertension, elevated urine protein levels, anemia, and underlying glomerular disease, contribute to CKD progression. In addition to conservative treatment, several medications are available to combat the progression of CKD to end-stage kidney disease. Renin-angiotensin-aldosterone system blockers could slow the progression of CKD by reducing glomerular hyperfiltration, lowering blood pressure, and decreasing inflammation. Mineralocorticoid receptor antagonists inhibit the mineralocorticoid receptor signaling pathway, thereby attenuating inflammation and fibrosis. Sodium-glucose cotransporter 2 inhibitors exhibit protective effects on the kidneys and against cardiovascular events. Tolvaptan, a selective vasopressin V2-receptor antagonist, decelerates the rate of increase in total kidney volume and deterioration of kidney function in patients with rapidly progressive autosomal dominant polycystic kidney disease. The protective effects of AST-120 remain controversial. Due to a lack of evidence regarding the efficacy and safety of these medications in children, it is imperative to weigh the benefits and adverse effects carefully. Further research is essential to establish the efficacy and safety profiles in pediatric populations.

• The Korean Journal of Food And Nutrition
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• v.36 no.6
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• pp.572-580
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• 2023

Hypertension is characterized by excessive renin-angiotensin system activity, leading to blood vessel constriction. Several synthetic compounds have been developed to inhibit renin and angiotensin-converting enzyme (ACE). These drugs often have adverse side effects, driving the exploration of plant protein-derived peptides as alternative or supplementary treatments. This study assessed the phenolic compound and amino acid content and the antioxidant and antihypertensive activity of 5 South Korean staple crops. Sorghum had the highest phenolic compound content and exhibited the highest antioxidant activity. Millet grains, particularly finger millet (38.86%), showed higher antihypertensive activity than red beans (14.42%) and sorghum (17.16%). Finger millet was found to contain a large proportion of branched-chain, aromatic, and sulfur-containing amino acids, which are associated with ACE inhibition. In particular, cysteine content was positively correlated with ACE inhibition in the crops tested (r=0.696, p<0.01). This study confirmed that the amino acid composition was more correlated with the antihypertensive activity of grains than the phenolic compound content. Finger millet mainly contained amino acids, which have higher ACE inhibitory activity, resulting in the strongest antihypertensive activity. These findings underscore the antihypertensive potential of select crops as plant-based food ingredients, offering insight into their biological functions.

• Journal of Dairy Science and Biotechnology
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• v.27 no.2
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• pp.17-23
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• 2009

In the light of the increasing concern over the prevalence of osteoporosis, hypertension, diabetes mellitus, we performed this study to review the correlation between the dietary calcium and vitamin D intake and these diseases. To this end, we investigated the effects of dietary calcium and vitamin D on these diseases. We observed that the intake of dietary calcium and vitamin D had a negative correlation with the incidences of osteoporosis, hypertension, and diabetes mellitus. Further, the intake of these two nutrients is expected to improve related mechanisms such as the renin-angiotensin system. Therefore, we suggest that dietary calcium and vitamin D have a beneficial effect on these diseases.

• Environmental Analysis Health and Toxicology
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• v.20 no.1
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• pp.39-45
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• 2005

Renin-angiotensin system (RAS)은 혈압 조절에 중요한 역할을 수행하는 생리적 조절계로써, 이 system 을 구성하는 유전자들의 이상은 본태성 고혈압의 발병과 유의하게 관련된 것으로 알려졌다. RAS의 주요한 구성 성분인 angiotensin II는 2종류의 수용체인 angiotensin II type I receptor(AT₁R)와 angiotensin II type I receptor(AT₂R)에 의해 그 효과가 매개되기 때문에, 이 수용체를 암호하는 유전자는 본태성 고혈압의 유력한 후보 유전자라고 볼 수 있다. 현재가지의 연구에 의하면, AT₁R 유전자에 존재하는 유전적 변이와 본태성 고혈압과의 관련성에 관해서는 많은 보고들이 있었지만, AT₂R 유전자에 존재하는 유전적 변이 가 본태성 고혈압에 유의한 효과를 나타내는 지에 관해서는 이렇다할 연구 성과가 별로 없는 실정이다. 이에 본 연구에서는 한국인 집단을 대상으로 하여, AT₂R 유전자에 존재하는 C3123A 다형성이 한국인 집단에서 본태성 고혈압과 유의한 관련성이 있는 지를 분석하였다. 이 유전자는 인간의 X 염색체에 존재하기 때문에, 여성인 경우에는 CC, CA및 AA로 이루어진 3유전자형이 존재하지만, 남성인 경우에는 C와 A로 이루어진 2종류의 대립 유전자로 구성되어 있기 때문에, 본 연구에서는 남성과 여성을 개별적으로 나누어서 분석하였다. 연구 결과, AT₂R 유전자에 존재하는 C3123A 다형성은 남녀 모두에서 본태성 고혈압과 유의한 관련성을 나타내지 않았다(P>0.05). 그렇지만, 이 다형성에 대한 대립 유전자 빈도를 서양인 집단과 비교했을 경우에는, 한국인을 대상으로 한 본 연구에서 A 대립 유전자 빈도가 0.33인 반면에 서양인 집단은 그 빈도가 0.43～0.48로 한국인 집단보다 높은 값을 나타내었다. 따라서, AT₂R 유전자에 존재하는 C3123A 다형성과 본태성 고혈압과의 관련성에 대해서는 한국인과 유전적 배경이 다른 서양인 집단을 대상으로 한 추시가 필요할 것으로 사료된다.

• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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• pp.364-375
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• 2011

Given that single blockade with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can achieve only partial and undurable suppression of the Renin Angiotensin System (RAS), it has been hypothesized that dual blockage would be more beneficial in the management of blood pressure (BP) reduction and prevention of progressive chronic kidney disease (CKD) than either agent alone. Thus, it has been suggested that the combination of an ACEI and an ARB might provide renal benefits to hypertensive patients over and above BP reduction. However, this might also expose patients to additive or synergistic side effects. We attempted to conduct a systematic review to evaluate the benefits and harms of combination therapy in hypertensive patients with or without kidney diseases. MEDLINE and KoreaMed were searched for relevant randomized clinical trials in adult hypertensive patients with or without diabetes (restricted to 1997, limited to trials published in English). Results were summarized using the random-effects model, and between-studies heterogeneity was estimated with $I^2$. A final analysis of ten trials (23,928 patients) revealed that the combination of an ACEI and an ARB reduced blood pressure (SBP/DBP) by 3.95/2.02 mmHg (95% confidence interval [CI], -4.38 to -3.53/-2.33 to -1.71) compared with ACEI monotherapy, and 2.83/2.64 mmHg (95% CI, -3.25 to -2.41/-4.95 to -0.33) compared with ARB monotherapy. Eight trials (391 patients) demonstrated a significant reduction in 24h-proteinuria (weighted mean difference, 0.16 g/day, 95% CI, -0.26-0.05), but they did not translate into an improvement in GFR. Tests for heterogeneity showed no difference in effect among the studies. The combination therapy reduced proteinuria by 30% (95% CI, 23% to 37%) and 39% (95% CI, 31% to 48%) compared with ACEI monotherapy and ARB monotherapy, respectively. However, in patients who had proteinuria more than 0.5 g/day, the combination therapy failed to show significant reduction in urinary protein excretion. The current cumulative evidence suggests that diabetic patients with proteinuria on dual RAS blockade have an increase risk of adverse events such as hyperkalemia, hypotension, and so on, compared with ACEI or ARB alone. It is, therefore, proposed that the combination therapy should not be routinely used for the treatment of hypertension with or without compelling indications.

• Journal of Preventive Medicine and Public Health
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• v.53 no.6
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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.

• Journal of Biomedical and Translational Research
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• v.19 no.4
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• pp.86-91
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• 2018

Angiotensin receptor blockers, such as telmisartan, are considered effective in the treatment of hypertension and proteinuria due to chronic kidney disease (CKD) in cats. It selectively blocks the $AT_1$ receptor and does not affect the $AT_2$ receptor, thus effectively blocking the activity of the renin angiotensin aldosterone system. This study aims to compare over time the changes in various indicators, including systemic hypertension and proteinuria, before and after the administration of telmisartan in cats with CKD. Decrease in blood pressure (BP) (p<0.001) and urine protein to creatinine (UP/C) ratio (p<0.001) were found to be statistically significant over time after the administration of telmisartan. BP and the UP/C ratio were $160{\pm} 22.2$ and $0.50{\pm}0.647$ before telmisartan administration (Day 0), $150{\pm}21.0$ and $0.27{\pm}0.487$ on the 30th day (Day 30), $150{\pm}17.0$ and $0.25{\pm}0.376$ on the 60th day (Day 60), and $140{\pm}17.8$ and $0.15{\pm}0.233$ on the 90th day (Day 90) after administration, respectively. BP and UP/C were statistically significantly lower in cats with CKD over time at each time point from Day 0 to Day 90 at 30 day intervals. Especially after 90 days of telmisartan administration, the improvement of BP and UP/C were estimated to be about 20 mmHg and 0.35, respectively. In conclusion, the oral administration of telmisartan to cats with CKD is effective in improving BP and proteinuria, which has a positive effect on long-term survival in cats with CKD.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.72-76
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• 2001

Essential hypertension is a heterogeneously multifactorial disease in which blood pressure is harmfully high without overt cause. Both genetic and environmental factors have been implicated in its etiology. In view of the regulatory role of this peptide in the carbohydrate metabolism and renin-angiotensin system, amylin gene has been proposed to a candidate gene for essential hypertension. Therefore, we scanned the amylin gene for mutations in 133 Korean normotensives and 61 essential hypertensives by single-strand conformational polymorphism, and found a single heterozygous S20G missense mutation. However, no significant difference was observed between normotensives and essential hypertensives in the distribution of allele and genotype frequencies of this mutation at the amylin gene (P>0.05). This finding suggests that S20G missense mutation of the amylin gene are unlikely to contribute to the etiology of essential hypertension in the Korean population.

• Korean Journal of Food Science and Technology
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• v.46 no.3
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• pp.375-383
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• 2014

This study aimed to investigate the effects of 50% ethanol extract of ripe black raspberry (Rubus occidentalis, RBR) on hypertension in human umbilical vein endothelial cells (HUVECs) and in spontaneously hypertensive rats (SHR). Angiotensin converting enzyme (ACE) inhibition and activation of nitric oxide production by endothelial nitric oxide synthase were significantly regulated by RBR in HUVEC cells. Moreover, the SHR showed significantly higher levels of blood pressure, ACE, renin, endothelin-1, and interleukin-6 than Wistar Kyoto rats (WKY). However, treatment with captopril and RBR decreased the levels of these hypertension-related events in the SHR. The renal arteriole showed greater media thickness/lumen diameter (%) in the SHR than in the WKY. However, media thickness/lumen diameter (%) was reduced in SHR by treatment with captopril and RBR. In addition, the number of eosinophilic cardiac muscle cells was decreased in the heart muscles after treatment with captopril and RBR. Therefore, this study suggests that 50% ethanol extract of RBR may be useful for the prevention and treatment of high blood pressure.

• Toxicological Research
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• v.17
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• pp.289-292
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• 2001

Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. Models of essential hypertension have been produced by mutated genes relating renin angiotensin system. The most significant contribution to understanding the genetic etiology of essential hypertension is probably the demonstration that discrete alterations in the expression of a variety of different genes can individually cause changes in the blood pressures of mice, even when the mice have all their compensatory mechanisms intact. These effects are readily detected in animals having moderate decreases in gene function due to heterozygosity for gene disruptions or modest increases due to gene duplication. As a species the mouse is highly resistant to atherosclerosis. However. through induced mutations it has been possible to develop lines oj mice that are deficient in apolipoprotein E, a ligand important in lipoprotein clearance, develop atherosclerotic lesions resembling those observed in humans. The atherosclerotic lesions in apoE-deficient mice have been well characterized, and they resemble human lesions in their sites of predilection and progression to the fibroproliferative stage. Other promising models are mice that are deficient in the low-density lipoprotein receptor. Considerable work still remains to be done in dissecting out in a rigorous manner the effects of alterations in single genes on the induction or progression of atherosclerosis and on the control of blood pressures. Perhaps even more exciting is the opportunity now becoming available to breed animals in which the effects oj precise differences in more than one gene can be studied in combination.