• Title, Summary, Keyword: angiotensin II

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Computer Simulation of Angiotensin II Binding to Its Receptor for de novo Lead Search

  • Kim, Dooil;Youngdo Won
    • Proceedings of the Korean Biophysical Society Conference
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    • pp.23-23
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    • 1996
  • A working molecular model of the angiotensin II type 1 receptor is built based on the seven transmembrane helix structure of the recently refined bacteriorhodopsin atomic coordinates. A multiple copy simultaneous search (MCSS) method is used to search the pharmacophore of angiotensin on the surface of the receptor. Multiple copies of amino acid fragments and organic functional groups are scattered around the possible binding site and the time dependent. (omitted)

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Angiotensin II-Induced Generation of Reactive Oxygen Species Is Regulated by a Phosphatidylinositol 3-Kinase/L-Type Calcium Channel Signaling Pathway (Angiotensin II에 의해 유도되는 활성산소발생 기전에 대한 연구)

  • Jin, Seo Yeon;Ha, Jung Min;Kim, Young Whan;Lee, Hye Sun;Bae, Sun Sik
    • Journal of Life Science
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    • v.25 no.2
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    • pp.231-236
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    • 2015
  • Angiotensin II (AngII) is an essential hormone that affects vascular physiology. For example, stimulation of vascular smooth muscle cells (VSMCs) rapidly induces vasoconstriction and results in the up-regulation of blood pressure. Chronic stimulation of VSMCs with AngII also results in hypertrophy. In this study, we confirmed an involvement of phosphatidylinositol 3-kinase (PI3K)-dependent calcium mobilization in AngII-induced generation of reactive oxygen species (ROS). Stimulation of rat aortic smooth muscle cells (RASMCs) with AngII significantly induced the generation of ROS in a dose- and time-dependent manner. AngII-induced generation of ROS was completely abolished by pharmacological inhibition of PI3K (with LY294002), but inhibition of the ERK signaling pathway had no effect. AngII-induced calcium mobilization was completely blocked by inhibition of PI3K, whereas inhibition of the ERK signaling pathway by PD98059 was ineffective. Depletion of extracellular calcium or inhibition of the L-type calcium channel by nifedipine completely blocked AngII-induced calcium mobilization. Depletion of extracellular calcium by EGTA and incubation of RASMCs with calcium-free medium both significantly blocked AngII-induced ROS generation. Inhibition of the L-type calcium channel also significantly blocked AngII-induced ROS generation. These results suggest that AngII-induced ROS generation is regulated by calcium mobilization, which, in turn, is modulated by a PI3K/L-type calcium channel signaling pathway.

The Relationship between Body Mass Index(BMI), Adipocyte Size and Leptin and Angiotensin II Secretion in Human Adipose Tissue

  • Heo Young-Ran;Moustaid-Moussa Naima
    • Journal of Community Nutrition
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    • v.8 no.2
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    • pp.69-75
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    • 2006
  • Adipose tissue has now been recognized as a rich source of metabolically active molecules that include leptin and angiotensinogen (AGT), the precursor of angiotensin II (Ang II). Both of which have been implicated in the pathogenesis of metabolic alteration and hypertension associated with obesity. In this study, we examined the relationship between body mass index (BMI), adipocyte size, leptin, Ang II secretion and mRNA expression in human adipose tissue obtained from female subjects. Leptin and Ang II were analyzed using specific radioimmunoassay kits following a 48hour tissue culture. Leptin and Ang II secretion varied from 1.4 - 72.1ng/g and 0.8 - 57.3pg/g of tissue respectively. These large individual variations limit significant correlation between BMI, leptin and Ang II secretion. Ang II secretion was significantly higher in the obese than the non-obese (p < 0.05) and positively correlated with BMI. However, no difference in leptin secretion between the obese and the non-obese was observed and leptin secretion showed negative correlation with BMI. No difference in leptin and AGT mRNA expression in adipose tissue between the obese and the non-obese was observed. Although several limitations of this study, we found increased Ang II secretion in obese patients compared with non-obese patients, and positive correlation between AGT and BMI. Observed difference in AGT expression between the obese and the non-obese in this study might be of importance in relation with obesity related hypertension. (J Community Nutrition 8(2): 69-75, 2006)

Duck Oil-loaded Nanoemulsion Inhibits Senescence of Angiotensin II-treated Vascular Smooth Muscle Cells by Upregulating SIRT1

  • Kang, Eun Sil;Kim, Hyo Juong;Han, Sung Gu;Seo, Han Geuk
    • Food Science of Animal Resources
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    • v.40 no.1
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    • pp.106-117
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    • 2020
  • Cellular senescence is associated with age-related vascular disorders and has been implicated in vascular dysfunctions. Here, we show that duck oil-loaded nanoemulsion (DO-NE) attenuates premature senescence of vascular smooth muscle cells (VSMCs) triggered by angiotensin II (Ang II). Compared with control nanoemulsion (NE), DO-NE significantly inhibited the activity of senescence-associated β-galactosidase, which is a biomarker of cellular senescence, in Ang II-treated VSMCs. SIRT1 protein expression was dose- and time-dependently induced in VSMCs exposed to DO-NE, but not in those exposed to NE, and SIRT1 promoter activity was also elevated. Consistently, DO-NE also dose-dependently rescued Ang II-induced repression of SIRT1 expression, indicating that SIRT1 is linked to the anti-senescence action of DO-NE in VSMCs treated with Ang II. Furthermore, the SIRT1 agonist resveratrol potentiated the effects of DO-NE on VSMCs exposed to Ang II, whereas the SIRT1 inhibitor sirtinol elicited the opposite effect. These findings indicate that DO-NE inhibits senescence by upregulating SIRT1 and thereby impedes vascular aging triggered by Ang II.

Isolation of Angiotensin I Converting Enzyme (ACE) Inhibitor from fermented oyster, Crassostrea gigas

  • Park, Ji-Young;Je, Jae-Young;Park, Pyo-Jam;Kim, Se-Kwon
    • Proceedings of the Korean Society of Fisheries Technology Conference
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    • pp.193-194
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    • 2002
  • Angiotensin I converting enzyme (ACE) inhibitor was purified from Crassostrea gigas. The ACE belongs to the class of metalloprotease. This enzyme plays an important physiological role in regulating blood pressure of the rennin-angiotensin system by converting from angiotensin I to octapeptide angiotensin II, a potent vasoconstrictor and by inactivating bradykinin, which has depressor action. (omitted)

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A Study on the Effect of the Dendropanax Mobifera Extract on Anti-Hypertensive (황칠나무 추출물이 고혈압에 미치는 영향에 관한 연구)

  • Jo, Yong-Bok;Lee, Jang-Hoon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.11
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    • pp.708-715
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    • 2016
  • This study examined the effects of an extract of Dendropanax morbifera on blood pressure, Angiotensin II, Angiotensin Converting Enzyme, Aldosterone, and lipid levels of spontaneously hypertensive rats. The groups were as follows: Control group, Hypertension control group, Water extract treated group, Ethanol extract treated group, n- hexane fraction treated group, Ethyl acetate fraction treated group, n- butanol fraction treated group, and Water fraction treated group. The blood pressure, and Angiotensin II, and Angiotensin Converting Enzyme, and Aldosterone levels were lower in the Ethyl acetate fraction treated group than in the hypertension control group. The change in blood pressure was lower in the Water extract treated group, Ethyl acetate fraction treated group, Ethanol extract treated group, n- hexane fraction treated group, and n- butanol fraction treated group than the hypertension control group. The concentration of Angiotensin II was lower in the Ethyl acetate fraction treated group, Ethanol extract treated group, n- hexane fraction treated group, and n- butanol fraction treated group than the hypertension control group(p<0.05). The level of Angiotensin Converting Enzyme was lower in the Ethyl acetate fraction treated group, Ethanol extract treated group, n- hexane fraction treated group, and n- butanol fraction treated group than the hypertension control group. The concentration of Aldosterone was lower in the Ethyl acetate fraction treated group, and n- butanol fraction treated group than the hypertension control group(p<0.05). In addition, the concentration lower in the Water extract treated group, Ethanol extract treated group, n- hexane fraction treated group than the hypertension control group. Overall, the effect of the Dendropanax morbifera extracts might be useful as anti-hypertensive, and functional food agents.

Expression of Class I and Class II a/b Histone Deacetylase is Dysregulated in Hypertensive Animal Models

  • Kee, Hae Jin;Kim, Gwi Ran;Lin, Ming Quan;Choi, Sin Young;Ryu, Yuhee;Jin, Li;Piao, Zhe Hao;Jeong, Myung Ho
    • Korean Circulation Journal
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    • v.47 no.3
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    • pp.392-400
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    • 2017
  • Background and Objectives: Dysregulation of histone deacetylase expression and enzymatic activity is associated with a number of diseases. It has been reported that protein levels of histone deacetylase (HDAC)1 and HDAC5 increase during human pulmonary hypertension, and that the enzymatic activity of HDAC6 is induced in a chronic hypertensive animal model. This study investigated the protein expression profiles of class I and II a/b HDACs in three systemic hypertension models. Materials and Methods: We used three different hypertensive animal models: (i) Wistar-Kyoto rats (n=8) and spontaneously hypertensive rats (SHR; n=8), (ii) mice infused with saline or angiotensin II to induce hypertension, via osmotic mini-pump for 2 weeks, and (iii) mice that were allowed to drink L-$N^G$-nitro-L-arginine methyl ester (L-NAME) to induce hypertension. Results: SHR showed high systolic, diastolic, and mean blood pressures. Similar increases in systolic blood pressure were observed in angiotensin II or L-NAME-induced hypertensive mice. In SHR, class IIa HDAC (HDAC4, 5, and 7) and class IIb HDAC (HDAC6 and 10) protein expression were significantly increased. In addition, a HDAC3 protein expression was induced in SHR. However, in L-NAME mice, class IIa HDAC protein levels (HDAC4, 5, 7, and 9) were significantly reduced. HDAC8 protein levels were significantly reduced both in angiotensin II mice and in SHR. Conclusion: These results indicate that dysregulation of class I and class II HDAC protein is closely associated with chronic hypertension.

Nephron Heterogeneity of Renin Release in Rat Kidney Slices: Effects of L-Isoproterenol, Angiotensin II and TMB-8

  • Seul, Kyung-Hwan;Kim, Suhn-Hee;Koh, Gou-Young;Cho, Kyung-Woo
    • The Korean journal of physiology & pharmacology
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    • v.25 no.1
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    • pp.61-67
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    • 1991
  • In order to determine possible relationships between the renin-angiotensin system and nephron heterogeneity, we compared the response of renin release and the angiotensin-converting enzyme (ACE) activity from different areas of the rat kidney. We used the renal cortical slices from the capsular surface to the juxtamedullary junction. Slices from outer one-third of the cortex were designated as outer cortical slices (OC), middle one-third as midcortical slices (MC), and inner one-third as inner cortical slices (IC). The renal renin content markedly decreased from OC and MC to IC. The basal lenin release was higher in OC than in MC or IC. On the contrary the percent change of renin release in response to L-isoproterenol was significantly higher in MC than in OC or IC. By TMB-8, the renin release in MC by $231{\pm}21%$ was higher than OC by $171{\pm}19%$ or IC by $$162{\pm}19. Angiotensin II suppressed renin release in OC and MC by $68{\pm}2,\;71{\pm}4%$ respectively, but only $40{\pm}7%$ in IC. The ACE activity was higher in IC than in OC, MC, medulla and papilla. The present data indicate that renin content and basal lenin release gradulally decreased from outer (OC) to inner (IC) cortex. The renin release in response to beta-adrenergic agonist, L-isoproterenol and intracellular calcium antagonist, TMB-8 were higher in MC than in OC and IC, but angiotensin II suppressed renin release less in IC than in OC and MC. It is suggested that juxtaglomerular cells of outer, mid-and inner cortices show a difference in renin release response to the stimuli.

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The Different Expression Patterns of HSP22, a Late Embryogenesis Abundant-like Protein, in Hypertrophic H9C2 Cells Induced by NaCl and Angiotensin II

  • Sung, Jae Hwi;Song, Ahran;Park, Taegun;Kim, Eunyoung;Lee, Seunggwan
    • Electrolytes & blood pressure
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    • v.16 no.1
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    • pp.1-10
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    • 2018
  • Background: High-NaCl diet is a contributing factor for cardiac hypertrophy. The role of HSP22 as a protective protein during cardiac hypertrophy due to hypernatremia is unclear. Accordingly, this study aimed to establish a cellular hypernatremic H9C2 model and to compare the expression of HSP22 in $Ca^{2+}$ homeostasis between a high-NaCl and angiotensin II-induced hypertrophic cellular H9C2 model. Methods: Real-time PCR was performed to compare the mRNA expression. Flow cytometry and confocal microscopy were used to analyze the cells. Results: The addition of 30 mM NaCl for 48 h was the most effective condition for the induction of hypertrophic H9C2 cells (termed the in vitro hypernatremic model). Cardiac cellular hypertrophy was induced with 30 mM NaCl and 1 ?M angiotensin II for 48 h, without causing abnormal morphological changes or cytotoxicity of the culture conditions. HSP22 contains a similar domain to that found in the consensus sequences of the late embryogenesis abundant protein group 3 from Artemia. The expression of HSP22 gradually decreased in the in vitro hypernatremic model. In contrast to the in vitro hypernatremic model, HSP22 increased after exposure to angiotensin II for 48 h. Intracellular $Ca^{2+}$ decreased in the angiotensin II model and further decreased in the in vitro hypernatremic model. Impaired intracellular $Ca^{2+}$ homeostasis was more evident in the in vitro hypernatremic model. Conclusion: The results showed that NaCl significantly decreased HSP22. Decreased HSP22, due to the hypernatremic condition, affected the $Ca^{2+}$ homeostasis in the H9C2 cells. Therefore, hypernatremia induces cellular hypertrophy via impaired $Ca^{2+}$ homeostasis. The additional mechanisms of HSP22 need to be explored further.

Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood Pressure Via Inhibition of p66shc Activation

  • Kang, Gun;Lee, Yu Ran;Joo, Hee Kyoung;Park, Myoung Soo;Kim, Cuk-Seong;Choi, Sunga;Jeon, ByeongHwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.5
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    • pp.467-472
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    • 2015
  • Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I ($AT_1R$) inhibitor, valsartan ($10{\mu}M$), but not by the $AT_2R$ inhibitor, PD123319. TSA ($1{\sim}10{\mu}M$) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing $AT_1R$. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through $AT_1R$.