• The Korean Journal of Physiology
• /
• v.29 no.2
• /
• pp.259-267
• /
• 1995

The renin-angiotensin system plays an important role in the regulation of blood pressure and in body fluid homeostasis. There is increasing evidence for generation of endogenous angiotensin II in many organs and for its role in paracrine functions. Studies were designed to investigate whether hemorrhage produces rapid changes in the gene expression of angiotensinogen in peripheral and brain tissues. Wistar rats received saline drinking water for 7 days, were bled at a rate of $3\;ml\;kg^{-1}\;min^{-1}$ for 7 min, and then decapitated 0, 2, 4, 8, or 24 hr after hemorrhage. Hemorrhage produced a produced hypotension with tachycardia at $2{\pm}8\;hr$, but blood pressure and heart rate had not fully recovered to the basal level at 24 hr. Plasma renin concentration was significantly increased at 2, 4, and 8 hr (maximum sixfold increase at 4 hr) and had returned to the basal level at 24 hr. Renal renin content was significantly increased only at 4 hr after hemorrhage. Angiotensinogen mRNA in both the kidney and liver were stimulated at 2 to 8 hrs, but recovered to the basal level at 24 hr. On the other hand, angiotensinogen mRNA levels il the hypothalamus and brainstem were continuously increased from 2 to 24 hrs. The present study demonstrates the presence of angiotensinogen mRNA in both hepatic and extrahepatic tissues, and more importantly, their up-regulation after hemorrhage. These results suggest that the angiotensinogen-generating systems in the liver, kideny and brain are, at least in part, under independent control and play a local physiological role.

• The Korean Journal of Physiology and Pharmacology
• /
• v.3 no.3
• /
• pp.315-320
• /
• 1999

Molecular regulation of the renin-angiotensin system (RAS) was investigated in deoxycorticosterone acetate (DOCA)-salt hypertension. The expression of renin, angiotensinogen and angiotensin II receptor genes in the kidney and liver was determined by Northern blot analysis in rats which were made DOCA-salt hypertensive over the period of 2 or 4 weeks. Along with the hypertension, renin mRNA was decreased in the remnant kidney. The expression of angiotensinogen gene was not significantly altered in the kidney, but was significantly decreased in the liver. The expression of angiotensin II receptor gene was increased in the kidney, while it remained unaltered in the liver. The duration of hypertension did not affect the altered gene expression. It is suggested that the components of RAS are transcriptionally regulated in DOCA-salt hypertension in a tissue-specific manner.

• Clinical and Experimental Pediatrics
• /
• v.52 no.1
• /
• pp.36-43
• /
• 2009

urpose : The renin-angiotensin system (RAS) has been demonstrated to play a major role in regulating blood pressure. Therefore, components of the RAS are likely candidate genes that may predispose an individual to essential hypertension and cardiovascular complications. Among them, the M235T polymorphism of the angiotensinogen gene has been speculated to be associated with elevated circulating angiotensinogen concentrations and essential hypertension. This study aimed to analyze the angiotensinogen M235T polymorphism in hypertensive adolescents and investigate its relationship with cardiovascular risks. Methods : Forty Korean hypertensive adolescents (aged 16-17, systolic $BP{\geq}140 mmHg$ and/or diastolic $BP{\geq}90 mmHg$) and fifty seven normal adolescents were included. Obesity index (OI), body mass index (BMI) were calculated. BP was measured by oscillometric methods in resting state. Polymerase chain reaction (PCR) technique was performed on DNA from the hypertensives subjects to analyze the M235T polymorphism. Serum homocysteine, insulin, renin, aldosterone and angiotensin converting enzyme (ACE) were tested according to each genotype. The carotid intima-media thickness (IMT) and carotid artery diameter, Pulse wave velocity (PWV) and ankle-brachial index (ABI) were measured according to each genotype. Results : Genotype frequencies of T/T, M/T and M/M were 62.5%, 35.0%, 2.5%, respectively in hypertensive adolescents. The results were not significantly different compared to control group. Serum insulin, renin levels, BMI and OI were significantly higher in thoses with the M/M genotype as compared to those with the T/T of M/T genotype. Conclusion : This study showed that the M235T polymorphism was not associated with essential hypertension or any cardiovascular risks. Further clinical research is required to ascertain the relationship between this polymorphism and cardiovascular complications in Korean hypertensive adolescents.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.6
• /
• pp.771-778
• /
• 1998

To investigate interaction of angiotensin converting enzyme (ACE) inhibitor with local tissue renin- angiotensin system (RAS), changes in gene expression of the RAS components in various tissues in response to chronic administration of an ACE inhibitor, enalapril, were examined in Sprague-Dawley male rats. Enalapril was administered in their drinking water $(3{\sim}4\;mg/day)$ over 8 wk. Plasma and renal ACE activity increased significantly after 4 and 8 wk of enalapril treatment. Renin levels of the plasma and kidney of the enalapril-treated rats markedly increased after 4 wk and decreased thereafter, but still remained significantly higher than those of control rats. Kidney mRNA levels of renin markedly increased after 4 and 8 wk of enalapril treatment, but those of angiotensinogen and ANG II-receptor subtypes, $AT_{1A}$ and $AT_{1B}$, did not change significantly. The liver expressed genes for renin, angiotensinogen and $AT_{1A}$ receptor subtype, but $AT_{1B}$ receptor subtype mRNA was not detectable by RT-PCR. None of mRNA for these RAS components in the liver changed significantly by enalapril treatment. The hypothalamus showed mRNA expressions of renin, angiotensinogen, $AT_{1A}$ and $AT_{1B}$ receptor subtypes. $AT_{1A}$ receptor subtype mRNA was more abundant than $AT_{1B}$ receptor subtype in the hypothalamus as shown in the kidney. However, gene expression of the RAS components remained unchanged during 8-wk treatment of enalapril. In the present study, chronic ACE inhibition increased plasma and renal levels of ACE and renin, but did not affect mRNA levels of other RAS components such as angiotensinogen, ANG II receptor subtypes in the kidney. Gene levels of the RAS components in the liver and hypothalamus were not altered by chronic treatment of enalapril. These results suggest the differential expression of the RAS components in response to enalapril, and localized action and some degree of tissue specificity of enalapril.

• The Journal of Korean Medicine
• /
• v.24 no.4
• /
• pp.102-112
• /
• 2003

The homozygous deletion allele of the angiotensin converting enzyme gene (ACF/DD), homozygous threonine allele of the angiotensinogen gene (AGN/TT), and the 4 allele of the apolipoprotein E gene (apoE/4) are reported to be associated with ischemic heart disease. Ischemic cerebrovascular disease (ICVD) is another atherosclerotic disease, and the effects of these polymorphisms on ICVD have been confusing. In this study, I investigated whether ACF/DD, AGN/TT, and apoE/4 genotypes are associated with ICVD and whether genetic risk is enhanced by the effect of one upon another. I ascertained these genotypes in patients with ICVD (n=121) diagnosed by brain computed tomography. Control subjects for the ICVD were randomly selected from subjects matched for age, gender, and history of hypertension with patients. Frequency of ACF/DD genotype was somewhat higher in the patients with ICVD than in the controls (18％ vs. 15％). Incidence of ICVD was higher in subjects with the apoE/4/4 genotype than in the other genotypes (50％ vs. 27-29％). Incidence of ICVD was much higher in subjects with the AGN/TT genotype than in AGN/MM genotype (36％ vs. 17％). Furthermore, the AGN/TT genotype greatly increased the relative risk for ICVD in the subjects with ACF/DD genotype (80.0％ vs. 20.0％, P=0.089). Finally, incidence of ICVD was much higher in the subjects with both apoE/2/4 and AGN/TT genotype than in the other genotypes (83.3％ vs. 16.7％, P=O.095). These results suggest that AGN/TT enhances the risk for ICVD associated with ACF/DD and apoE/2/4.

• The Korean Journal of Physiology and Pharmacology
• /
• v.1 no.2
• /
• pp.151-159
• /
• 1997

In an attempt to investigate whether hemorrhage affects the gene expression of the renin-angioteusin system (RAS) components in the brain and peripheral angiotensin-generating tissues, changes in mRNA levels of the RAS components in response to hemorrhage were measured in conscious unrestrained rats. Wistar rats were bled at a rate of 3 ml/kg/min for 5 min, and then decapitated 7 h after hemorrhage. Levels of mRNA for renin, angiotensinogen and angiotensin $II-AT_1$ receptor subtypes ($AT_{1A}$ and $AT_{1B}$) were determined with the methods of northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Hemorrhage produced a profound hypotension with tachycardia, but blood pressure and heart rate recovered close to the basal level at 7 h. Plasma and renal renin levels were significantly increased at 7 h. Hemorrhage induced rapid upregulation of gene expression of both $AT_{1A}$ and $AT_{1B}$ receptor subtypes in the brainstem and hypothalamus, downregulation of them in the adrenal gland and liver. However, renin mRNA level increased in the brainstem, decreased in the liver, but was not changed in the hypothalamus, kidney and adrenals after hemorrhage. Angiotensinogen mRNA level was not significantly changed in any of the tissue except a slight increase in the liver. The kidney and liver did not show any significant change in gene expression of the RAS components. These results suggest that gene expression of the RAS in central and peripheral tissues are, at least in part, under independent control and the local RAS in each organ plays specific physiologic role.

• Molecules and Cells
• /
• v.37 no.6
• /
• pp.487-496
• /
• 2014

Angiotensinogen (AGT), the precursor of angiotensin I, is known to be involved in tumor angiogenesis and associated with the pathogenesis of coronary atherosclerosis. This study was undertaken to determine the role played by AGT in endothelial progenitor cells (EPCs) in tumor progression and metastasis. It was found that the number of EPC colonies formed by AGT heterozygous knockout ($AGT^{+/-}$) cells was less than that formed by wild-type (WT) cells, and that the migration and tube formation abilities of $AGT^{+/-}$ EPCs were significantly lower than those of WT EPCs. In addition, the gene expressions of vascular endothelial growth factor (VEGF), Flk1, angiopoietin (Ang)-1, Ang-2, Tie-2, stromal derived factor (SDF)-1, C-X-C chemokine receptor type 4 (CXCR4), and of endothelial nitric oxide synthase (eNOS) were suppressed in $AGT^{+/-}$ EPCs. Furthermore, the expressions of hypoxia-inducible factor (HIF)-$1{\alpha}$and $-2{\alpha}$ were downregulated in $AGT^{+/-}$ early EPCs under hypoxic conditions, suggesting a blunting of response to hypoxia. Moreover, the activation of Akt/eNOS signaling pathways induced by VEGF, epithelial growth factor (EGF), or SDF-$1{\alpha}$ were suppressed in $AGT^{+/-}$ EPCs. In $AGT^{+/-}$ mice, the incorporation of EPCs into the tumor vasculature was significantly reduced, and lung tumor growth and melanoma metastasis were attenuated. In conclusion, AGT is required for hypoxia-induced vasculogenesis.

• 대한예방의학회:학술대회논문집
• /
• 2001.04a
• /
• pp.89-89
• /
• 2001

• Proceedings of the Korean Society of Fisheries Technology Conference
• /
• 2001.10a
• /
• pp.171-172
• /
• 2001

체내에 널리 분포되어 있는 angiotensin 전환효소(angiotensin converting enzyme, ACE ; peptidyldipeptide hydrolase, EC 3.4.15.1)는 angiotensinogen이 renin의 특이적 분해를 받아서 생성된 불활성형인 angiotensin I의 말단 dipeptide(His-Leu)를 절단하여 octapeptide인 활성형의 angiotensin II로 전환시키며, 이렇게 생성된 angiotensin II는 직접적으로 혈압상승 작용을 하거나 adrenal로부터 sediumretaining steroid hormone인 aldosterone의 유리를 촉진시켜 체내 나트륨을 저류시킨다. (중략)

• Proceedings of the Korean Society of Fisheries Technology Conference
• /
• 2001.10a
• /
• pp.97-98
• /
• 2001

순환기계 질병의 원인이 되는 동시에 뇌출혈, 심장병 및 신장병 등과 합병증으로 나타날 경우 치사율이 매우 높은 만성 퇴행성 질환인 고혈압의 90％ 이상을 차지하는 본태성 고혈압은 정상적인 혈압을 유지하는 기구들이 천천히 붕괴되어 진행되는 질병이다(Frohlich, 1982). 이러한 본태성 고혈압의 원인 중에서 reninㆍangiotensin계가 혈압조절에 매우 중요한 역할을 한다고 알려지고 있다(Saxena, 1992). 즉, angiotensinogen이 renin의 분해를 받아서 angiotensin I을 생성하는데, 이는 angiotensin converting enzyme(ACE)에 의하여 COOH 말단의 dipeptide가 절단되어 강력한 혈관수축작용을 하는 angiotensin II를 생성한다. (중략)