• Journal of Preventive Medicine and Public Health
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• v.39 no.2
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• pp.177-183
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• 2006

Objectives : In this study we examined the association between the genetic markers ACE (A-240T, C-93T, I/D, A2350G), AGT (M235T), AT1R (A1166C), CYP11B2 (T344C, V386A), REN (G2646A), ADRB2 (G46A, C79G, T47C, T1641), GNB3 (C825T) and ADD1 (G460W) and the presence of essential hypertension in adolescents. Methods : The Kangwha Study is an 18-year prospective study that is aimed at elucidating the determinants of the blood pressure level from childhood to early adulthood. For this study, we constructed a case-control dataset of size of 277 and 40 family trios data from the Kangwha Study. For this purpose, we perform a single locus-based case-control association study and a single locus-based TDT (transmission/disequilibrium test) study. Results : In the case-control study, the single locus-based association study indicated that the ADD1 (G460W) (p=0.0403), AGT (M235T) (p=0.0002), and REN (G2646A) (p=0.0101) markers were significantly associated with the risk of hypertension. These results were not confirmed on the TDT study. This study showed that genetic polymorphisms of the ADD1, AGT and REN genes might be related to the hypertension in Korean adolescents. Conclusions : This study provided useful information on genetics markers related to blood pressure. Further study will be needed to confirm the effect of the alpha adducin gene, the angiotensinogen gene and the renin gene on essential hypertension.

• Kidney Research and Clinical Practice
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• v.37 no.4
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• pp.347-355
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• 2018

Background: Nephrotic syndrome (NS) is the most common glomerulopathy in children. Acute kidney injury (AKI) is a common complication of NS, caused by severe intravascular volume depletion, acute tubular necrosis, interstitial nephritis, or progression of NS. However, the incidence and risk factors of childhood-onset NS in Korea are unclear. Therefore, we studied the incidence, causes, and risk factors of AKI in hospitalized Korean patients with childhood-onset NS. Methods: We conducted a retrospective review of patients with childhood-onset NS who were admitted to our center from January 2015 to July 2017. Patients with decreased renal function or hereditary/secondary NS, as well as those admitted for management of other conditions unrelated to NS, were excluded. Results: During the study period, 65 patients with idiopathic, childhood-onset NS were hospitalized 90 times for management of NS or its complications. Of these 90 cases, 29 met the Kidney Disease Improving Global Outcomes criteria for AKI (32.2%). They developed AKI in association with infection (n = 12), NS aggravation (n = 11), dehydration (n = 3), and intravenous methylprednisolone administration (n = 3). Age ${\geq}9$ years at admission and combined use of cyclosporine and renin-angiotensin system inhibitors were risk factors for AKI. Conclusion: AKI occurred in one-third of the total hospitalizations related to childhood-onset NS, owing to infection, aggravation of NS, dehydration, and possibly high-dose methylprednisolone treatment. Age at admission and use of nephrotoxic agents were associated with AKI. As the AKI incidence is high, AKI should be considered during management of high-risk patients.

• 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.

• Journal of Pharmacopuncture
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• v.22 no.2
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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.

• Endocrinology and Metabolism
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• v.33 no.4
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• pp.485-492
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• 2018

Background: Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA. Methods: Forty-two patients (mean age $48.8{\pm}10.9$ years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins. Results: The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was $8.9{\pm}0.3mg/dL$ (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ${\rho}=-0.424$, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (${\beta}=-0.366$, P=0.068 and ${\beta}=-0.252$, P=0.070, respectively). Conclusion: Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.

• Nutrition Research and Practice
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• v.15 no.2
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• pp.160-172
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• 2021

BACKGROUND/OBJECTIVES: Nutritional status and food intake during pregnancy and lactation can affect fetal programming. In the current metabolic syndrome epidemic, high-fructose diets have been strongly implicated. This study investigated the effect of maternal high-fructose intake during pregnancy and lactation on the development of metabolic syndrome in adult offspring. SUBJECTS/METHODS: Drinking water with or without 20% fructose was administered to female C57BL/6J mice over the course of their pregnancy and lactation periods. After weaning, pups ate regular chow. Accu-Chek Performa was used to measure glucose levels, and a tail-cuff method was used to examine systolic blood pressure. Animals were sacrificed at 7 months, their livers were excised, and sections were stained with Oil Red O and hematoxylin and eosin (H&E) staining. Kidneys were collected for gene expression analysis using quantitative real-time Polymerase chain reaction. RESULTS: Adult offspring exposed to maternal high-fructose intake during pregnancy and lactation presented with heavier body weights, fattier livers, and broader areas under the curve in glucose tolerance test values than control offspring. Serum levels of alanine aminotransferase, aspartate aminotransferase, glucose, triglycerides, and total cholesterol and systolic blood pressure in the maternal high-fructose group were higher than that in controls. However, there were no significant differences in mRNA expressions of renin-angiotensin-aldosterone system genes and sodium transporter genes. CONCLUSIONS: These results suggest that maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome with hyperglycemia, hypertension, and dyslipidemia in adult offspring.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.493-505
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• 2023

In recent years, an increasing number of reports have explored the wound healing mechanism of these two traditional Chinese herbal medicines- Panax ginseng and Panax notoginseng, but there is no systematic research on the related core functions and different mechanisms in the treatment of wound healing up to now. Based on network pharmacology and meta-analysis, the present work aimed to comprehensively review the commonality and diversity of P. ginseng and P. notoginseng in wound healing. In this study, a wound healing-related "ingredients-targets" network of two herbs was constructed. Thereafter, meta-analysis of the multiple target lists by Metascape showed that these two medicines significantly regulated blood vessel development, responses to cytokines and growth factors and oxygen levels, cell death, cell proliferation and differentiation, and cell adhesion. To better understand the discrepancy between these two herbs, it was found that common signaling pathways including Rap1, PI3K/AKT, MAPK, HIF-1 and Focal adhesion regulated the functions listed above. In parallel, the different pathways including renin-angiotensin system, RNA transport and circadian rhythm, autophagy, and the different metabolic pathways may also explained the discrepancies in the regulation of the above-mentioned functions, consistent with the Traditional Chinese Medicine theory about the effects of P. ginseng and P. notoginseng.

• Journal of Pharmacopuncture
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• v.26 no.4
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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.

• Oncology Reports
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• v.43 no.2
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• pp.625-634
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• 2020

While exploring new angiogenesis inhibitors from microbial metabolites, we recently isolated ahpatinins C, E, and G from a soil-derived Streptomyces sp. 15JA150. Ahpatinins C, E and G are known to have pepsin and renin inhibitory activities; however, their antiangiogenic activities and underlying molecular mechanisms have not been fully elucidated. In the present study, the antiangiogenic properties of ahpatinins C, E and G were investigated. The results revealed that the natural compounds significantly inhibited the vascular endothelial growth factor (VEGF)-induced proliferation, invasion, adhesion, and tube formation of human umbilical vein endothelial cells (HUVECs) without exhibiting any cytotoxicity. It was also revealed that ahpatinin E effectively suppressed the neovascularization of the chorioallantoic membranes in growing chick embryos. Notably, ahpatinins C, E, and G led to the downregulation of VEGF-induced activation of VEGF receptor 2 (VEGFR2) and its downstream signaling mediators, including AKT, ERK1/2, JNK, p38, and NF-κB, in HUVECs. Moreover, they reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in the HUVECs following stimulation with VEGF. Furthermore, ahpatinins C, E, and G reduced the tumor cell-induced invasion and tube forming abilities of HUVECs, as well as the expression of VEGF, by suppressing hypoxia-inducible factor-1α (HIF-1α) activity in U87MG glioblastoma cells. Collectively, the present findings indicated that ahpatinins C, E, and G may be used in anticancer therapy by targeting tumor angiogenesis through the inhibition of both VEGFR2 and HIF-1α pathways.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.183-192
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• 2005

Purpose : The long term disease course and prognostic factors were evaluated in childhood Henoch-$Sch{\ddot{o}}nlein$ puruura nephritis(HSPN). Methods : A total of 75 children(44 boys and 31 girls) with HSPN were included in this study. The onset age was $8.0{\pm}3.1$ years(2.3-l5.3 years), and the follow-up period was $4.3{\pm}3.6$ years(1.0-17.1 years). Kidney biopsy was done in 24 children(32$\%$). Initial clinical and laboratory findings were evaluated. In addition, polymorphisms of the renin angiotensin system(RAS) genes(insertion/deletion in intron 16 of ACE gene, M235T in AGT gene, and A1166C in AGTR gene) were analysed. The initial and last clinical states were classified into 4 groups as follows A, normal; B, minor urinary abnormalities; C, active renal disease (nephrotic-range proteinuria and/or hypertension with serum creatinine $\leq$1.5 mg/dL); D, renal insufficiency. Results : At the onset, the clinical states of the patients were B in 26(35$\%$), C in 46(61$\%$), and D, in 3(4$\%$). The distribution of the RAS gene polymorphism of HSPN were not different from that of 100 healthy control subjects. At the last follow-up, the clinical states of the patients were A in 23(31$\%$), B in 38(50$\%$), C in 9(12$\%$), and D in 5(7$\%$). A multiple logistic regression identified age at the onset and initial urine protein excretion as significant prognostic factors. Analysis of genotypes of the 3 RAS genes as prognostic values revealed no statistical significance. Conclusion : Older age at onset and severe proteinuria were identified as poor prognostic factors of childhood HSPN. Implication of the RAS gene polymorphism In HSPN could not be validated in this small-scale retrospective study. (J Korean Soc Pediatr Nephrol 2005;9:183-192)