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atrial natriuretic peptide signal pathway upregulated in stomach of streptozotocin-induced diabetic mice

World Journal of Gastroenterology 2010年第1期16卷 48-55页

作者： Young-Chul Kim Department of Physiology Chungbuk National University College of Medicine

AIM:To investigate atrial natriuretic peptide(ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A)pathway and diabetic gastroparesis. METHODS:Male imprinting control region(ICR)mice (4 wk old)were divided into two groups:control mice, and streptozotocin-induced diabetic mice.Eight weeks after injection,spontaneous gastric contraction was recorded by using physiography in control and streptozotocin-induced diabetic mice.The ANP-positive cells in gastric mucosa and among dispersed gastric epithelial cells were detected by using immunohistochemistry and flow cytometry,respectively.ANP and natriureticpeptide receptor type A(NPR-A)gene expression in gastric tissue was observed by using the reverse transcriptase polymerase chain reaction. RESULTS:The frequency of spontaneous gastric contraction was reduced from 12.9±0.8 cycles/min in the control group to 8.4±0.6 cycles/min in the diabetic mice(n=8,P<0.05).However,the amplitude of contraction was not significantly affected in the diabetic group.The depletion of interstitial cells of Cajal in the gastric muscle layer was observed in the diabetic mice.ANP-positive cells were distributed in the gastric mucosal layer and the density index of ANP-positive cells was increased from 20.9±2.2 cells/field in control mice to 51.8±2.9 cells/field in diabetic mice(n=8, P<0.05).The percentage of ANP-positive cells among the dispersed gastric epithelial cells was increased from 10.0%±0.9%in the control mice to 41.2%± 1.0%in the diabetic mice(n=3,P<0.05).ANP and NPR-A genes were both expressed in mouse stomach, and the expression was significantly increased in the diabetic mice. CONCLUSION:These results suggest that the ANP/ NPR-A signaling pathway is upregulated in streptozotocin-induced diabetic mice,and contributes to the development of diabetic gastroparesis.

关键词： Diabetes mellitus atrial natriuretic peptide Gastric mucosa Gastroparesis

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atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats

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Chinese Medical Journal 2013年第4期126卷 747-750页

作者： ZHU Yao-bin ZHANG Yan-bo LIU Dong-hai LI Xiao-feng LIU Ai-jun FAN Xiang-ming QIA0 Chen-hui LING Feng LIU Ying-long Department of Pediatric Heart Center Beijing Anzhen Hospital Capital Medical University Beijing 100029 China Department of Pediatric Heart Center State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Disease Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China Department of Cardiovascular Surgery First Affiliated Hospital of Zhengzhou University Zhengzhou Henan 450052 China Department of Cardiothoracic Surgery Second Affiliated Hospital of Kunming Medical University Kunming Yunnan 650101 China

Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recognized that atrial natriuretic peptide （ANP） possesses a broad range of biological activities, including effects on endothelial function and inflammation. A recent study has revealed that ANP exerts anti-inflammatory effects. In this study we tested the effects of human ANP （hANP） on lung injury in a model of oleic acid （OA）-induced acute lung injury （ALl） in rats. Methods Rats were randomly assigned to three groups （n=6 in each group）. Rats in the control group received a 0.9% solution of NaCI （1 ml-kg-l.h1） by continuous intravenous infusion, after 30 minutes a 0.9% solution of NaCI （1 ml/kg） was injected intravenously, and then the 0.9% NaCI infusion was restarted. Rats in the ALl group received a 0.9% NaCI solution （1 ml-kgl-h-~） intravenous infusion, after 30 minutes OA was injected intravenously （0.1 ml/kg）, and then the 0.9% NaCI infusion was restarted. Rats in the hANP-treated ALl group received a hANP （0.1 IJg.kg-Lmin~） infusion, after 30 minutes OA was injected intravenously （0.1 ml/kg）, and then the hANP infusion was restarted. The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels. Results Serum interleukin （IL）-113, IL-6, IL-10 and tumor necrosis factor （TNF） a were increased in the ALl group at six hours. The levels of all factors were significantly lower in the hANP treated rats （P 〈0.005）. Similarly, levels of IL-113, IL-6, IL-10 and TNF-a were higher in the lung tissue in the ALl group at six hours, hANP treatment significantly reduced the levels of these factors in the lungs （P 〈0.005）. Histological examination revealed marked reduction in interstitial congestion, edema, and inflammation. Conclusion hANP can attenuate inflammation in OA-induced lung injury in rat model.

关键词： acute respiratory distress syndrome atrial natriuretic peptide inflammatory response cytokine rats

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Changes of atrial natriuretic peptide and antidiuretic hormone in children with postural tachycardia syndrome and orthostatic hypertension： a case control study

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Chinese Medical Journal 2014年第10期127卷 1853-1857页

作者： Zhao Juan Yang Jinyan Du Shuxu Tang Chaoshu Du Junbao Jin Hongfang Department of Pediatrics Peking University First Hospital Beijing100034 China Department of Pediatrics. Capital Medical University ShijitanHospital Beijing 100038 China Department of Physiology and Pathophysiology Peking UniversityHealth Sciences Centre Beijing 100191 China

Background The abnormal blood volume regulation is one of the most important pathogenesis in postural tachycardia syndrome in children.This study was designed to investigate the plasma atrial natriuretic peptide and antidiuretic hormone levels in postural tachycardia syndrome children,and their associations with the changes in heart rate and blood pressure in head-up test.Methods Twenty-one postural tachycardia syndrome patients （（12±2） years） and 26 healthy children （（12±1） years） were included.According to blood pressure changes in head-up test,the postural tachycardia syndrome patients were divided into two subgroups：postural tachycardia syndrome with orthostatic hypertension and postural tachycardia syndrome without orthostatic hypertension.The plasma atrial natriuretic peptide and antidiuretic hormone levels were measured using enzyme-linked immunosorbent assay.Results The plasma atrial natriuretic peptide level in postural tachycardia syndrome patients was higher than the control （P=0.004）,whereas the difference in plasma antidiuretic hormone level between postural tachycardia syndrome and controls was not significant （P=0.222）.The plasma antidiuretic hormone level of patients suffering from postural tachycardia syndrome with orthostatic hypertension was much higher than that of children having postural tachycardia syndrome without orthostatic hypertension （P ＜0.05）.In postural tachycardia syndrome patients,the updght max heart rate was positively correlated with the plasma atrial natriuretic peptide level （r=0.490,P＜0.05） and the upright systolic blood pressure was positively correlated with the plasma antidiuretic hormone levels （r=0.472,P ＜0.05）.Conclusions There was a disturbance of plasma atrial natriuretic peptide and antidiuretic hormone in postural tachycardia syndrome children.

关键词： postural tachycardia syndrome atrial natriuretic peptide antidiuretic hormone orthostatic hypertension

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Endogenous Endothelin-1 Regulates Hypoxia-Induced atrial natriuretic peptide Secretion by Activating the MAPK/ERK and PI3K/Akt Signaling Pathways in Isolated Beating Rabbit Atria

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Journal of Biosciences and Medicines 2016年第1期4卷 45-53页

作者： Chaochao Bian Dazhi Ding Honghua Jin Liping Liu Lan Hong Bairi Cui Xun Cui Department of Physiology School of Medicine Yanbian University Yanji China Institue of Clinical Medicine Yanbian University Yanji China Key Laboratory of Organism Functional Factors of the Changbai Mountain Ministry of Education Yanbian University Yanji China Cellular Function Research Center Yanbian University Yanji China

The present study investigated a possible mechanism for endogenous endothelin-1 (ET-1) regulation of atrial natriuretic peptide (ANP) secretion in isolated perfused acute hypoxic rabbit atria. Acute hypoxia significantly enhanced the release of ET-1 and the expression of the ET receptor (ETR) type A and B (ETRA and ETRB) in atrial tissues, with a concomitant increase in ANP secretion. The ETRA or ETRB antagonist, BQ123 (0.3 μmol/L) or BQ788 (0.3 μmol/L), respectively attenuated hypoxia-induced ANP secretion. Both antagonists significantly attenuated the levels of hypoxiainduced atrial phosphorylated (p)-extracellular signal-regulated kinase (ERK) and p-protein kinase B (Akt). The ERK and Akt inhibitors, PD098059 (30 μmol/L) and LY294002 (30 μmol/L), respectively mimicked the effect of the ETR antagonists. These results demonstrated that acute hypoxia- mediated atrial ET-1 regulated ANP secretion through ETR and the subsequent mitogenactivated protein kinase (MAPK)/ERK and ETR-phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. These pathways may mediate atrial endocrine functions under hypoxic conditions.

关键词： Hypoxia Endothelin-1 ET Receptor atrial natriuretic peptide Signaling Pathway

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Cardioprotective mechanism of atrial natriuretic peptide

Cardioprotective mechanism of atrial natriuretic peptide

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2012年中美临床和转化医学国际论坛心脑血管病分会论坛...

作者： Lan Hong1,Zhengai Chen2,Xun Cui1 1 Department of Physiology,College of Medicine,Yanbian University,Yanji,China 2 Department of Pharmacology,College of Medicine,Yanbian University,Yanji,China.

＜正＞Heart is no longer considered only as an efficient pump but also as an important endocrine organ, becausre the heart generates and secretes atrial natriuretic peptide（ANP）.It is well known that ANP have important biological effects,such as diuresis and natriuresis,modulating blood pressure and cardiovascular homeostasis by combining with natriuretic peptide receptors.ANP binds to NPR-A receptor which is a member of the membrane-bound guanylyl cyclase family and exerts its biological effects by increasing cGMP levels.

关键词： atrial natriuretic peptide Mitochondrial permeability transition pore Glycogen synthase kinase 3β Myocardial ischemia/reperfusion injury Protein kinase G Phosphoinositide 3-kinase/Akt

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Effects and safety of natriuretic peptides as treatment of cirrhotic ascites:A systematic review and meta-analysis

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World Journal of Hepatology 2022年第4期14卷 827-845页

作者： Rasmus Hvidbjerg Gantzel Mikkel Breinholt Kjær Peter Jepsen Niels Kristian Aagaard Hugh Watson Lise Lotte Gluud Henning Grønbæk Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus N 8200Denmark Gastroenterology Unit Copenhagen University HospitalHvidovre 2650Denmark Department of Clinical Medicine University of CopenhagenHvidovre 2650Denmark

BACKGROUND natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis,counterbalancing vasoconstriction and anti-natriuretic factors.The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies,and definitive results are lacking.AIM To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.METHODS We searched MEDLINE,Web of Science,Scopus,Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites.Inclusion was not limited by treatment duration or dose,or by follow-up duration.Both randomised controlled trials and non-randomised studies were eligible for inclusion.The primary outcome was change in renal sodium excretion.Secondary outcomes included safety measures and changes in renal water excretion,plasma aldosterone concentration,and plasma renin activity.RESULTS Twenty-two studies were included.atrial natriuretic peptide(ANP)was the only intensively studied treatment.Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of>30 ng/kg/min were administered compared with≤30 ng/kg/min(Pnatriuretic response to ANP was low,mainly due to small sample sizes and considerable between-study heterogeneity.D

关键词： atrial natriuretic peptide B-type natriuretic peptide Urodilatin Cirrhosis Ascites Refractory ascites

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QUINAPRILAT INCREASES TOTAL BODY VASCULAR COMPLIANCE IN RATS WITH MYOCARDIAL INFARCTION

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中华医学杂志(英文版) 1992年第5期105卷 382-389页

作者： Yongwei Chien Edward D. Frohlich Allan A. MacPhee Barbara L. Pegram Alton Ochsner Medical Foundation New Orleans LA 70121 USA

To test whether quinaprilat,a new angiotensinconverting enzyme inhibitor,has any venous effect,itsimmediate effects were measured on mean circulatoryfilling pressure(MCFP),intravascular volume and to-tal body vascular(i.e.,venous)compliance in consciousrats with mild congestive heart failure induced bycoronary artery ligation.MCFP was determined by in-flating a right atrial balloon to arrest the circulationinstantly and temporarily.Total body vascular compli-ance was derived from total circulatory pressure-vol-ume relationships as determined by seriesmeasurements of MCFP with different intravascularvolume status.In 8 rats with mean infarct size of26±4%,30-minute infusion of quinaprilat(0.1mg/kg/min)decreased both mean arterial andcentral venous pressures by 8 mmHg and 0.7 mmHg,respectively(P<0.02);heart rate,MCFP,hematocritand blood volume remained unchanged.Comparedwith control vehicle infusion,quinaprilat increased thetotal body vascular compliance(2.09±0.12 vs 2.69±0.23ml/kg/mmHg;P<0.05)and decreasedextrapolated unstressed circulating volume(34.96±1.10 vs 28.53±2.55ml/kg;P<0.02).These datasuggest that quinaprilat produces possible venodilationthrough immediately improved total body vascularcompliance thereby reducing cardiac preload in this ratmodel of chronic heart failure.

关键词： CONGESTIVE HEART-FAILURE CONVERTING ENZYME-INHIBITORS PRESSURE-VOLUME RELATIONSHIP atrial natriuretic peptide CONSCIOUS RAT NITROGLYCERIN CAPTOPRIL CAPACITY THERAPY MODEL

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Software-aided detection and structural characterization of cyclic peptide metabolites in biological matrix by high-resolution mass spectrometry

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Journal of Pharmaceutical Analysis 2020年第3期10卷 240-246页

作者： Ming Yao Tingting Cai Eva Duchoslav Li Ma Xu Guo Mingshe Zhu Pharmaceutical Candidate Optimization Bristol-Myers SquibbPrincetonNJUSA XenoBiotic Labs WuXi AppTecNanjingChina SCIEX ConcordONL4K 4V8Canada MassDefect Technologies PrincetonNJUSA

Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigidity.However,cyclic peptides could form numerous putative metabolites from potential hydrolytic cleavages and their fragments are very difficult to interpret.These characteristics pose a great challenge when analyzing metabolites of cyclic peptides by mass spectrometry.This study was to assess and apply a software-aided analytical workflow for the detection and structural characterization of cyclic peptide metabolites.Insulin and atrial natriuretic peptide(ANP)as model cyclic peptides were incubated with trypsin/chymotrypsin and/or rat liver S9,followed by data acquisition using TripleTOF?5600.Resultant full-scan MS and MS/MS datasets were automatically processed through a combination of targeted and untargeted peak finding strategies.MS/MS spectra of predicted metabolites were interrogated against putative metabolite sequences,in light of a,b,y and internal fragment series.The resulting fragment assignments led to the confirmation and ranking of the metabolite sequences and identification of metabolic modification.As a result,29 metabolites with linear or cyclic structures were detected in the insulin incubation with the hydrolytic enzymes.Sequences of twenty insulin metabolites were further determined,which were consistent with the hydrolytic sites of these enzymes.In the same manner,multiple metabolites of insulin and ANP formed in rat liver S9 incubation were detected and structurally characterized,some of which have not been previously reported.The results demonstrated the utility of software-aided data processing tool in detection and identification of cyclic peptide metabolites.

关键词： atrial natriuretic peptide Metabolism of cyclic peptide High resolution mass spectrometry Insulin Software-aided data processing

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Decorin Induces Cardiac Hypertrophy by Regulating the CaMKⅡ/MEF-2 Signaling Pathway In Vivo

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Current Medical Science 2021年第5期41卷 857-862页

作者： Yan YANG Wei-wei YU Wen YAN Qin XIA Department of Geriatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading,but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure.Cardiac hypertrophy is mostly considered reversible,and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension,but also achieves therapeutic effects by blocking fibrosis-related signaling pathways.However,the mechanism of action of decorin remains unknown and unconfirmed.Methods:We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight,histological analysis and immunohistochemistry.Western blotting was performed to detect the expression levels of CaMKⅡ,p-CaMKⅡ and MEF-2 in the heart.Results:Our results confirmed that decorin can regulate the CaMKⅡ/MEF-2 signaling pathway,with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy.Conclusion:Taken together,the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKⅡ/MEF-2 signaling pathway in vivo,revealing a new therapeutic approach for the prevention of cardiac hypertrophy.

关键词： decorin cardiac hypertrophy calcium/calmodulin-dependent protein kinaseⅡ myocyte enhancer factor 2 atrial natriuretic peptide

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ANPT2238C,C-664G Gene Polymorphism and Coronary Heart Diseasein Chinese Population

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2006年第5期26卷 528-530页

作者：张利芸程龙献何美安胡丙长邬堂春 Institute of Cardiovascular Disease Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Institute of Occupational Medicine Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

The association between atrial natriuretic peptide （ANP） polymorphism and coronary heart disease （CHD） was studied in Chinese population. The genotypes of ANP T2238C and ANP C-664G were detected by polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP） methods in 158 consecutive CHD patients and 165 controls. It was found that the distribution of A2A2 genotype in CHD group was significantly higher than that in control group （P〈0.05）. Stepwise Logistic regression analysis revealed that male, smoking, history of hypertension, history of diabetes, family history of hypertension, high level of serum cholesterol, and ANP T2238C polymorphism were the possible risk factors in patients with CHD （P〈0.05）. However, there was no significant difference between the patients with CHD and the control group in the distribution of ANP C-664G polymorphism （P〉0.05）. The results suggest that A2A2 T2238C genotype could be one of the risk factors for CHD （P〈0.05, OR： 1.80, 95 % CI： 1.03-3.15）.

关键词： coronary heart disease atrial natriuretic peptide polymorphism

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