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Acute Effects of Tolvaptan on Renal Hemodynamics in Autosomal Dominant Polycystic Kidney Disease —A Randomized, Cross-Over, Double Blind, Placebo-Controlled Study of Renal Plasma Flow and Glomerular Filtration Rate

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Open Journal of Nephrology 2019年第4期9卷 97-114页

作者： My Helbo Malmberg Frank Holden Mose Rikke Lund Sonderbaek June Anita Ejlersen Jens Jorgen Jensen Erling Bjerregaard Pedersen Jesper Norgaard Bech University Clinic in Nephrology and Hypertension Regional Hospital Jutland WestHolstebroDenmark University of Aarhus AarhusDenmark Department of Nuclear Medicine Regional Hospital Jutland WestHolstebroDenmark

Background: Previous studies have shown that reduced renal plasma flow (RPF) may play a role in progression of renal disease in autosomal dominant polycystic kidney disease (ADPKD). Tolvaptan, a vasopressin 2 antagonist, reduces growth of total kidney volume and slows the decrease in estimated glomerular filtration rate (eGFR) in ADPKD. The purpose of this randomized, cross-over, double-blind, placebo-controlled study was to investigate if acute tolvaptan treatment increases RPF in ADPKD patients. Methods: Eighteen ADPKD patients (chronic kidney disease stages I-iiI) were investigated twice (min. 10 days apart) after acute treatment with either tolvaptan 60 mg or placebo. Two hours after treatment RPF and GFR were estimated by Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography. During the examination day, central and brachial blood pressures (BP) were measured using Mobil-O-Graph? PWA. We also measured plasma concentrations of vasopressin (p-AVP), renin (PRC), angiotensin ii (p-Angii) and aldosterone (p-Aldo), urine excretion of aquaporin 2 (u-AQP2), urine output (OU), urine osmolality (u-Osm) and fractional excretion of sodium (FENa). Results: 99-mTc-DTPA renography showed a similar RPF (673 ± 262 ml/min after tolvaptan vs. 650 ± 209 ml/min after placebo, p = 0.571) and GFR (78 ± 26 ml/min after tolvaptan vs. 79 ± 21 ml/min after placebo p = 0.774) after tolvaptan and placebo treatment. P-AVP and UO increased and u-Osm decreased after tolvaptan and remained unchanged during placebo. Systolic BP tended to decrease during renography during tolvaptan. Very small or insignificant changes were seen in PRC, p-Angii and p-Aldo. Conclusions: Acute tolvaptan treatment did not change renal hemodynamics in ADPKD.

关键词： Autosomal Dominant Polycystic Kidney Disease Renal Plasma Flow Glomerular Filtration Rate Renography Brachial Blood Pressure Central Blood Pressure Vasopressin Renin angiotensin ii Aldosterone

Molecular mechanisms and therapeutic perspectives of left ventricular hypertrophy in systemic hypertension

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South China Journal of Cardiology 2015年第4期16卷 256-261页

作者：陶沙谭宁冯颖青 Southern Medical University Guangdong Cardiovascular Institute Department of Cardiology Guangdong General Hospital

Background Left ventricular hypertrophy （LVH） induced by systemic hypertension represents a maladaptive response to the increased overload. However antihypertensive treatments are not always useful to regress or prevent LVH. Thoroughly understanding the mechanisms will help to find new therapeutic targets that prevent or reverse left ventricular hypertrophy. A number of regulators and molecular signaling pathways have been shown to be involved in the hypertrophic process, such as angiotensin ii, heat shock proteins 90, microRNAs, TRPC, mTOR, HDAC and PI3K/Akt signaling pathways. Therefore, other treatments, such as G1 cyclin antagonists, HSP90 inhibitor, Rho-kinase inhibitor, calcineurin blockers, CS866, statins, scutellarin, and aldosterone antagonist could prevent left ventricular hypertrophy.

关键词： left ventricular hypertrophy hypertension angiotensin ii heat shock proteins 90 PI3K/Aktsignaling pathways TRPC mTOR HDAC MicroRNA

EFFECT OF angiotensin Ⅱ RECEPTOR SUBTYPE ⅠON THE FIRING RATE IN CATECHOLAMINERGIC TUMOR CELLS

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Journal of Pharmaceutical Analysis 2003年第2期15卷 166-169页

作者：杜剑青孙成文唐敬师 Colin Sumners MohanK Raizada Department of Physiology Medical School of Xi’an Jiaotong University Department of Physiology College of MedicineUniversity of Florida

Objective To study the action of brain angiotensin Ⅱ(Ang Ⅱ) receptors and underlying intracellular mechanism in the catecholaminergic system Methods Action potentials (APs) of the primary co cultured catecholaminergic tumor (CATH.a) cells were recorded with the whole cell patch clamp configuration in current clamp mode. Expression of Ang Ⅱ receptors subtypes (AT 1 and AT 2 ) was detected by RT PCR technique. Results The differentiated CATH.a cells represented a neuron like characterization. All CATH.a cells expressed mRNA encoding both Ang Ⅱ AT 1 and AT 2 receptor subtypes. Ang Ⅱ increased the firing rate in the CATH.a cells, which was inhibited completely by addition administration of the AT 1 but not AT 2 receptor antagonist, and partially by using the inhibitors of signal molecules, U73122 (10 μmol·L -1 ), or KN 93 (10 μmol·L -1 ), or calphostin C (10 μmol·L -1 ). Conclusion Ang Ⅱ increases firing rate in CATH.a cells via AT 1 receptor. The CATH.a cells expressing functional AT 1 and AT 2 receptor subtypes may be of general utility for the study of the Ang Ⅱ receptor induced modulation of brain catecholaminergic system.

关键词： angiotensin ii CATH.a cell AT 1 receptor cell firing spark

Effects on Cell Viability and on Apoptosis in Tumoral(MCF-7)and in Normal(MCF10A)Epithelial Breast Cells after Human Chorionic Gonadotropin and Derivated-angiotensin Peptides Treatments

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Journal of Cancer Therapy 2013年第7期4卷 65-69页

作者： Silvana Aparecida Alves Correa de Noronha Werica Bernardo Alexandre Jesus Barros Clovis Ryuichi Nakaie Suma Imura Shimuta Ismael Dale Cotrim Guerreiro da Silva Samuel Marcos Ribeiro de Noronha Laboratorio de Cirurgia Translacional Departamento de CirurgiaUniversidade Federal De Sao Paulo/Escola Paulista De MedicinaSao PauloBrazil Laboratorio de Ginecologia Molecular Universidade Federal de Sao PauloSao PauloBrazil Departamento de Biofísica Universidade Federal de Sao PauloSao PauloBrazil

angiotensin-(1 - 7) [Ang-(1 - 7)] is an endogenous heptapeptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apoptotic properties of Ang-(1 - 7) and of Ang-(1 - 7)-substituents 9-fluorenylmethyloxycarbonyl (Fmoc) e Ang ii-derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) in normal (MCF10A) and in tumoral (MCF7) epithelial mammary cell lines. Both cell lines received an hCG and angiotensin peptides 24-hour treatment, in combination or alone followed by cell viability, apoptosis and cell cycle assays performed by flow cytometer (GUAVA). After hCG, Ang-(1 - 7), hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments, MCF7 displayed cell viability decrease and mid-apoptosis increase. We also observed cell viability decrease in MCF10A after Ang-(1 - 7), Ang-(1 - 7) Fmoc and hCG + Angii Toac treatments. These cells had an increase in late apoptosis and necrosis after Angii Toac, hCG + Ang-(1 - 7) and hCG + Ang-(1 - 7)-Fmoc treatments. Regarding the cell cycle analysis, we did not observed any changes in cell cycle phases. In summary, cell viability was decreased and apoptosis (initial, mid and late) was increased after hCG and/or Ang-(1 - 7) peptides treatments. These results point out hCG and Ang-(1 - 7) as effective compounds to inhibit cell proliferation, since they decrease cell viability and increase apoptosis in both normal and in tumoral breast cells, being the effect more pronounced in the tumoral cell line. Our results support the idea of investigating more closely the putative use of these compounds as novel therapeutic agents for breast cancer.

关键词： angiotensin ii angiotensin 1-7 angiotensin ii Type 1 Receptor(AT1R) Breast Cancer Apoptosis Human Chorionic Gonadotropin

Effect of Ligustrazine on Activity Changes of angiotensin Ⅱ in Plasma and Cerebrospinal Fluid in Patients with Vascular Dementia

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Chinese Journal of Integrated Traditional and Western Medicine 2003年第1期9卷 16-20页

作者：李强王景周张莉莉高唱周红杰高东 Department of Neurology Daping HospitalThe Third Military Medical UniversityChongqing 400042

Objective: To study the relationship between the activity changes of angiotensin ii (Ang ii ) in plasma, cerebrospinal fluid (CSF) and the pathophysiology of vascular dementia (VD) on the one hand and the therapeutic effects of ligustrazine (LIG) on VD and its mechanisms on the other hand. Methods: Case grouping: VD group with 50 cases (26 VD patients treated with LIG and 24 with Ginaton) ; cerebral infarction (CI) group with 62 cases (routine therapy was given) and control group (without organic disease in central nervous system) with 26 cases. Investigation method ? To test cognitive function by Mini-Mental State Examination (MMSE), Functional Activities Questionnaire (FAQ), Hachinski Ischemic Scale (HIS) and P300 peak latency (P300PL) . To measure the concentration of Angii by radioimmunoassay (RIA) technology. Results: As compared with CI recovery phase or with control group, Angii levels in CSF were markedly increased in VD group(Pii in plasma or CSF were markedly lowered (P0.05) . Conclusion: Angii activity changes plays an important role in pathophysiological process of VD. LIG can improve cognitive function in VD. It may be correlated with improving of the disorders of Ang ii in central nervous system.

关键词： vascular dementia angiotensin ii ligustrazine

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附睾局部组织肾素血管紧张素系统(英文)

Developmental and Reproductive Biology 1998年第2期 71-78页

作者：陈小章梁宝成黄宜定香港中文大学医学院生理系

附睾内液体微环境对精子的成熟和贮藏是相当重要的。附睾液体的形成取决于附睾上皮的吸收与分泌功能，而先前的实验已经证明：这些吸收与分泌的活动是受到除神经激素以外旁分泌与自分泌的调控。虽然肾素血管紧张素系统（ＲＡＳ）在很多... 详细信息

附睾内液体微环境对精子的成熟和贮藏是相当重要的。附睾液体的形成取决于附睾上皮的吸收与分泌功能，而先前的实验已经证明：这些吸收与分泌的活动是受到除神经激素以外旁分泌与自分泌的调控。虽然肾素血管紧张素系统（ＲＡＳ）在很多组织上旁分泌与自分泌的作用已多有报导，但其在附睾的存在及作用仍鲜为人知。本综述总结了本实验室在这方面的研究结果，通过使用不同的实验方法，例如，免疫组织化学，放射免疫分析，分子生物学及短路电流电生理学方法，我们得到的结果显示了ＲＡＳ主要成员在附睾的分布（Ｆｉｇ．１）和表达，并阐明了血管紧张素ＩＩ对附睾阴离子分泌的调控作用（Ｆｉｇｓ．２＆３）。本综述还就血管紧张素ＩＩ对附睾旁分泌与自分泌的作用及其机制（Ｆｉｇ．４），以及对精子功能的作用进行了讨论。

关键词： epididymis anion secretion angiotensin ii epithelium AT 1 and AT 2 receptors

ANG Ⅱ-AT1R axis facilitated CD11+Ly6Chi cells differentiation/polarization into M1-like macrophage dependent on Erk1/2 or p38-Stat3 pathway and involved in EAM

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ANG Ⅱ-AT1R axis facilitated CD11+Ly6Chi cells differentiati...

Antihypertrophic effect of ginsenoside Rg1 on cardie myocytes and its medianisms

第十二届全国免疫学学术大会

作者： Lv Hongxiang Wu Yan Shao Xiaoyi Zhou Shanshan Chen Rong Jiang Yuanyuan Xu Huaxi Su Zhaoliang Jiangsu University

Macrophage,a high plasticity population,is widely distributed.Macrophage functions are settled and acquired polarization programs in response to microenvironmental signals and involved in many inflammatory disorders,s... 详细信息

关键词： angiotensin ii Experimental autoimmune myocarditis Macrophage Thl7 cells

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Antihypertrophic effect of ginsenoside Rg1 on cardie myocyte...

Effects of i.c.v. losartan on the angiotensin Ⅱ-mediated pressor responses and c-fos expression in near-term ovine fetus

第十五届国际药理学大会

作者： Ying-Ting Wang Xie-Nan Huang An-sheng Sun Jing-Shan Shi Department of Pharmacology Zunyi Medical College Zunyi 563003. China

＜正＞ To study the potential inhibitory effect of ginsenoside Rg1 （Rg1） on myocardial hypertrophy,the cardiac myocyte hypertrophy model was indused by Ang ii-0.1μmol·L-1, and the cell diameter,protein content and the expression of atrial natriuretic peptide （ANP） mRNA were used as hypertrophic parameters. For mechanism studies,the intracellular free Ca2 + concentration （[ Ca2 + ]i）, the nitric oxide （NO） content in culture medium and the expressions of ANP- , cal-cineurin （CaN） - and eNOS-mRNA were detected. The results showed that Rg1 （12.5 - 50 μg ml-1） concentration-dependently reduced the increased cell diameter,protein content and the expression of ANP mRNA and increased the NO content and eNOS mRNA expression. Further more. Rg1 could remarkably decrease the elevated [Ca2 + ]i and CaN mRNA expression induced by Ang ii. NG-nitro-Larginine ester could abolish the antihypertrophic effect of Rb1. It is concluded Rg1 inhibit the cardiomyocyte hypertrophy induced by Ang n. which may be related to its inhibitory effect on [Ca2+ ]i. promoting effect on NO formation,and involved in CaN signal pathway.

关键词： angiotensin ii ginsenoside Rg1 caidic myocyte hypertrophy calcineurin

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Effects of i.c.v. losartan on the angiotensin Ⅱ-mediated pr...