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Background: The study on pathogenesis of acute pancreatitis has become a hot spot in clinical research, and the role of nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome in the pathogenesis of acute pancreatitis is not fully clear. Aims: To investigate the correlation between serum levels of endothelin (ET), nitric oxide (NO) and NLRP3 inflammasome in patients with acute pancreatitis. Methods: A total of 120 patients with acute pancreatitis from July 2016 to July 2018 at Longhua District People's Hospital of Shenzhen were selected as the observation group. According to the severity of disease, the patients in observation group were divided into mild group, moderate group and severe group. Fifty healthy subjects were served as controls. The serum levels of ET and NO were detected by radioimmunoassay. The serum level of NLRP3 inflammasome was detected by enzyme linked immunosorbent assay. Pearson correlation test was used to analyze the correlation between levels of ET, NO and NLRP3 inflammasome in patients with acute pancreatitis. Results: The serum levels of ET, NO and NLRP3 inflammasome in the observation group were significantly higher than those in the control group (P<0.05). The levels of ET, NO and NLRP3 inflammasome in the observation group increased with the increase of disease severity (P<0.05). Pearson correlation analysis showed that levels of ET and NO in patients with acute pancreatitis were positively correlated with NLRP3 inflammasome level (P<0.05). Conclusions: The levels of serum ET, NO and NLRP3 inflammasome are significantly increased in patients with acute pancreatitis, and are significantly correlated with the severity of disease, indicating that serum NLRP3 inflammasome may participate in the occurrence and development of acute pancreatitis.
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Objective To observe the effect of β-blocker on dilated cardiomyopathy (DCM) in children.Methods Sixty-one children cases of DCM in this hospital from 1995 to 2015 were retrospectively analyzed and divided into the treatment group(taking β-blocker,n=35) and control group(non-taking β-blocker,n=26) according to whether taking β-blocker.The clinical effect of β-blocker was preliminarily observed.Results The heart rate,LVDD,LVSD and LA after treatment in the treatment group were significantly decreased compared with before treatment(P＜0.05),while EF was significantly increased(P＜0.05);LVDD after treatment in the control group was significantly decreased(P＜0.05),while hear rate,RV,LVDD,LVSD,LA,MV and EF had no obvious change compared with before admission(P＞0.05).The heart rate,LVDD,LVSD and EF after treatment had statistical difference between the treatment group and control group (P＜0.05),the heart function after treatment in the treatment group was significantly improved compared with the control group (P＜0.05).The heart function improvement degree after treatment in the patients with hypertension of the treatment group was significantly better than those with normal blood pressure(P＜0.05).DCM with hypertension was significantly improved after treatment and was better than DCM without hypertension (P＜0.05).The The heart function improvement degree after treatment in the patients with carvedilol treatment was obviously better than that in the patients with metoprolol treatment(P＜0.05).Conclusion β-blocker could be used in the treatment of DCM,its effect is especially good in DCM children patients with hypertension,in which the effect of carvedilol is better than that of metoprolol.
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Cerebral autoregulation is a main mechanism of brain tissue maintains constant brain blood flow,which has important significance for the occurrence,development,and outcome of ischemic stroke.This article reviews the roles and mechanisms of endothelin system in cerebral blood flow regulation after ischemic stroke.
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Objective To observe the effect of β-blocker on dilated cardiomyopathy (DCM) in children.Methods Sixty-one children cases of DCM in this hospital from 1995 to 2015 were retrospectively analyzed and divided into the treatment group(taking β-blocker,n=35) and control group(non-taking β-blocker,n=26) according to whether taking β-blocker.The clinical effect of β-blocker was preliminarily observed.Results The heart rate,LVDD,LVSD and LA after treatment in the treatment group were significantly decreased compared with before treatment(P＜0.05),while EF was significantly increased(P＜0.05);LVDD after treatment in the control group was significantly decreased(P＜0.05),while hear rate,RV,LVDD,LVSD,LA,MV and EF had no obvious change compared with before admission(P＞0.05).The heart rate,LVDD,LVSD and EF after treatment had statistical difference between the treatment group and control group (P＜0.05),the heart function after treatment in the treatment group was significantly improved compared with the control group (P＜0.05).The heart function improvement degree after treatment in the patients with hypertension of the treatment group was significantly better than those with normal blood pressure(P＜0.05).DCM with hypertension was significantly improved after treatment and was better than DCM without hypertension (P＜0.05).The The heart function improvement degree after treatment in the patients with carvedilol treatment was obviously better than that in the patients with metoprolol treatment(P＜0.05).Conclusion β-blocker could be used in the treatment of DCM,its effect is especially good in DCM children patients with hypertension,in which the effect of carvedilol is better than that of metoprolol.
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Cerebral autoregulation is a main mechanism of brain tissue maintains constant brain blood flow,which has important significance for the occurrence,development,and outcome of ischemic stroke.This article reviews the roles and mechanisms of endothelin system in cerebral blood flow regulation after ischemic stroke.
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OBJECTIVE: To investigate the effect of enhanced external counterpulsation (EECP) on plasma nitric oxide (NO), Endothelin 1 (ET1), high sensitive C-reactive protein (HSCRP) and quality of life (QoL) in patients with coronary artery disease (CAD). METHODS: We conducted a pilot randomized clinical trial in order to evaluate plasma NO, ET1, HSCRP and QoL before and after twenty sessions of EECP (group A) and cardiac rehabilitation (CR, group B) in 42 patients with CAD (21 in each group). RESULTS: Forty-two patients (33 male and 9 female) were included in the study. The mean age was 58.2+/-10 years. The mean HSCRP was 1.52+/-0.7 in the EECP group and it was reduced to 1.27+/-0.4 after intervention. The reduction in HSCRP was not statistically significant in EECP and CR groups with p=0.33 and p=0.27, respectively. There was not significant improvement of NO, ET1, and QoL in the EECP and CR groups shortly after therapy (p>0.05). CONCLUSION: Although the short-term EECP treatment in CAD patients improved HSCRP, NO, ET1, and QoL compared with the baseline those improvements are not statistically significant. Further studies are necessary with large study groups and more sessions.
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Humans , Male , C-Reactive Protein , Coronary Artery Disease , Counterpulsation , Endothelin-1 , Endothelins , Nitric Oxide , Pilot Projects , Plasma , Quality of Life , RehabilitationABSTRACT
Objective To investigate the influence of irbesartan and hydrochlorothiazide on the serum inflammatory factors (CRP ,IL‐6) ,Hcy ,endothelin and hemorheology levels in the patients with hypertension .Methods 148 cases of essential hyperten‐sion were divided into the research group (n=74) and the control group (n=74) according to the random grouping method .The control group was treated by the conventionally symptomatic therapy ,while on this basis the research group was given with the irbesartan and hydrochlorothiazide therapy .The total treatment course of 2 groups were 3 months .The systolic pressure and dias‐tolic pressure ,serum CRP and IL‐6 ,plasma Hcy ,endothelin levels ,hemorheology indexes in the two groups were performed the contrastive analysis .The drug safety was evaluated .Results The systolic pressure and diastolic pressure after the treatments in the two groups were significantly decreased compared with before treatment(P0 .05);the ser‐um CRP and IL‐6 levels after treatment in the research group were significantly lower than those in the control group(P0 .05);the plasma Hcy and endothelin after treatment in the research group were significantly lower than those in the control group(P0 .05) .Conclusion Irbesartan and hydrochlorothiazide can significantly reduce the blood pressure ,serum inflammatory ,Hcy and endothelins levels in the patients with hypertension ,have no influence on the he‐morheologic indexes and no serious adverse reactions ,and are safe and reliable .
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Objective To evaluate the therapeutic effect of modifiedHuanglian-Jiedudecoction for resistant hypertension and explore its possible mechanism.Methods A total of 90 patients with resistant hypertension were recruited and randomly divided into a treatment group and a control group, 45 patients in each group. The control group was treated with oral administration of irbesartan and hydrochlorothiazide tablets and controlled-release nifedipine tablets, while the treatment group was further added modifiedHuanglian-Jiedu decoction for 4 weeks. Plasma endothelin (ET) and calcitonin gene-related peptide (CGRP) were measured by radioimmunoassay.Rusults The total efficiency according to the TCM syndrome in the treatment group was 86.7%(39/45) which was higher than 64.4%(29/45) in the control group(χ2=4.873,P=0.027). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased after the treatment in both groups ( SBP in the treatment group: 119.26 ± 9.34 mmHgvs.172.11 ± 10.52 mmHg,t=25.201,P<0.01; DBP in the treatment group: 78.18 ± 7.21 mmHgvs.111.12 ± 11.16 mmHg,t=16.631, P<0.01; SBP in the control group: 145.21 ± 7.56 mmHgvs.171.32 ± 11.15 mmHg,t=13.002,P<0.01; DBP in the control group: 93.57±8.13 mmHgvs. 109.89 ± 12.21 mmHg,t=7.463,P<0.01), while the decrease of SBP (t=14.487,P<0.01) and DBP (t=9.501, P<0.01) in the treatment group was more greater than those in the control group. The control rate of blood pressure in the treatment and control groups were 73.3% (33/45) and 55.6% (25/45), respectively, there had no significant difference (χ2=2.376,P=0.123). The plasma ET in the treatment group was significantly decreased than that in the control group (75.68 ± 10.67 ng/Lvs.112.79 ± 12.26ng/L;t=15.317,P<0.05), and CGRP significantly increased (49.87 ± 4.75 ng/Lvs.33.87 ± 7.89 ng/L;t=11.654,P<0.05).Conclusion Modified Huanglian-Jiedudecoction may have some therapeutic effect for resistant hypertension, its mechanism may be involved in ET decreasing and CGRP increasing.
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Objective To study the protective effect of lycopene (LP) against diabetic retinopathy (DR) in rats and its related mechanism. Methods A single dose of streptozotocin (56 mg/kg) was injected intraperitoneally in SD rats to induce diabetes retinopathy (DR), and the 20 successful DR models were equally randomized into DR group and LP treatment group. Meanwhile, 10 normal rats served as normal control group (NC). LP group received LP gavage (60 mg/kg) once a day; NC and DR groups were gavaged with equivalent saline daily for 8 weeks. The serum levels of endothelin(ET) and calcitonin gene related protein(CGRP) were detected by using radioimmunoassay (RIA), and the expression of vascular endothelial growth factor (VEGF) in the retina was determined by immunohistochemistry and Western blotting analysis. Results The serum levels of ET and expression of VEGF in the retina were significantly increased in DR groups when compared with NC group (P < 0.05), and the serum CGRP was significantly decreased (P < 0.05); Compared with DR group, LP group had significantly lower VEGF expression and ET levels and significantly higher level of CGRP (P < 0.05). Conclusion LP can protect against DR in rats by decreasing serum ET, increasing serum CGRP, and subsequent down-regulating VEGF expression.
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Objective:To observe the effect of Chinese herbal fumigation combined with three-step tuina manipulation on concentration of endothelin (ET) and calcitonin gene-related peptide (CGRP) and vertigo in patients with vertebral artery cervical spondylosis (VACS). Methods:A total of 120 eligible cases were randomly allocated into an observation group and a control group, 60 in each group. Cases in the observation group were treated with Chinese herbal fumigation combined with three-step tuina manipulation, whereas cases in the control group were treated with oral Flunarizine Hydrochloride Capsules. Results: After treatment, vertigo in both groups was alleviated; there were intra-group significant differences in ET decrease and CGRP increase (P Conclusion: Chinese herbal fumigation combined with three-step tuina manipulation can regulate the levels of ET and CGRP and improve vertigo in patients with VACS. Its therapeutic efficacy is superior to oral Flunarizine Hydrochloride Capsules.
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Objective To study the risk factors and clinical features on acute hepatic dysfunction induced by sepsis.Methods One hundred and sixty-eight patients with sepsis were divided into 2 groups according to liver function:simple sepsis group (control group,142 cases) and acute hepatic dysfunction induced by sepsis group (observation group,26 cases).The biochemical indicators,plasma endothelin (ET)-1,sepsis-related organ failure assessment (SOFA) were compared between 2 groups.The risk factors of inducing acute hepatic dysfunction were analyzed.Results The incidence of acute hepatic dysfunction in 168 patients with sepsis was 15.5％ (26/168).The total bilirubin,direct bilirubin,creatinine,range of blood glucose variation,arterial blood lactic acid,plasma ET-1,SOFA,fatality rate in observation group were significantly higher than those in control group [(35.9 ±9.8) μμmol/L vs.(27.8 ±6.7) μmol/L,(17.7 ± 8.0) μ mol/L vs.(12.3 ± 5.9) μ mol/L,(219.6 ± 156.4) μ mol/L vs.(159.4 ± 125.3) μ mol/L,(7.6 ±4.9) mmol/L vs.(3.0 ± 1.6) mmol/L,(3.8 ± 1.3) mmol/L vs.(2.0 ± 1.2) mmol/L,(79.6 ±25.7)μg/L vs.(60.8 ± 12.6) μg/L,(8.8 ±2.6) scores vs.(5.7 ± 1.8) scores,38.5％ (10/26) vs.17.6％(25/142)],there were statistical differences (P ＜ 0.01 or ＜ 0.05).Multifactor Logistic regression analysis results showed that long-term drinking,cardiac insufficiency and hypotension were independent risk factors of acute hepatic dysfunction induced by sepsis.Conclusions The arterial blood lactic acid,plasma ET-1 and SOFA in patients with acute hepatic dysfunction induced by sepsis are higher.Long-term drinking,cardiac insufficiency and hypotension are the risk factors of acute hepatic dysfunction induced by sepsis.
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Objective To investigate the effect of local mild hypothermia on the cerebral hemodynamic parameters,plasma Endothelin-1 (ET-1s) and calcitonin gene-related peptide (CGRPs) of the subarachnoid hemorrhage patients (SAH).Methods Sixty patients were divided randomly into local mild hypothermia group and control group (n =30 patients each group).The middle cerebral artery average blood flow rates (VMCAs) and pulse index (PIs) were detected with transcranial Doppler (TCD),plasma ET-1 s and CGRPs were tested on the D1,D7,D10,and D14,respectively.Results The VMCAs in the mild hypothermia group were lower on the D7,D10,and D14 [7 d:(95.46 ±22.48)cm/s vs (110.35 ±32.38) cm/s,t =2.07,P ＜ 0.05 ; 10 d:(85.57 ± 17.47) cm/s vs (97.64 ± 20.55) cm/s,t =2.45,P＜0.05 ;14 d:(57.16 ± 14.36)cm/s vs (70.56 ± 19.42) cm/s,t =3.04,P ＜ 0.01],PIs and plasma ET-1s were lower on the D10 and D14 compared with the control group [PIs:10 d:0.76 ±0.21 vs 0.88±0.25,t =2.01,P ＜0.05;14 d:0.72±0.18 vs 0.84 ±0.19,t =2.51,P ＜0.05] [ET-1s:10 d:(71.37 ± 16.63) pg/ml vs (81.46 ±21.38)pg/ml,t =2.04,P ＜0.05 ;14 d:(55.73 ± 15.18) pg/ml vs (68.28 ± 20.57) pg/ml,t =2.69,P ＜ 0.01].Plasma CGRPs were higher compared with the control group on the D7,D10,and D14 [7 d:(26.55 ±6.45)pg/ml vs (23.64 ±4.56)pg/ml,t =2.02,P ＜0.05;10 d:(24.15 ±7.35)pg/ml vs (20.52 ±6.18) pg/ml,t =2.07,P ＜0.05;14 d:(30.37 ±6.28)pg/ml vs (26.88 ± 4.39) pg/ml,t =2.49,P ＜ 0.05].Conclusions The mild hypothermia treatment could reduce the plasma ET-1s,improve plasma CGRPs,and improve the prognosis of the patients.
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Objective To investigate the relationship between the plasma levels of ET-1,TAT,and hs-CRP and slow coronary flow syndrome (SCFS),and explore effects of coronary endothelial function,coagulation function,and inflammatory reaction on blood flow of coronary artery.Methods A total of 400 cases with normal blood flow of coronary artery by coronary angiogram was randomly selected.The coronary flow patterns were determined by corrected thrombolysis in myocardial infarction frame count method (cT-FC).Among them,45 cases whose average cTFC more than 27 were assigned as SCFS group,the other 45 cases no SCFS.Plasma levels of ET-1,TAT and hs-CRPwere examined with enzyme-linked immunosorbent assay (ELISA),and were compared between two groups.Moreover,multivariate analysis evaluating predictors of SCFS was performed with regression test.Results No statistical difference was found between two groups concerning the gender,history of hypertension,diabetes mellitus,and cigarette alcohol percentage..The plasma level of HDL in SCFS group was lower than that of no SCFS [(1.22 ± 0.42) mmol/L vs (1.44±0.34) mmol/L,t =-2.731,P ＜0.01],but the plasma level of glucose in the former was higher than that of the latter [(5.68 ±0.62) mmol/L vs (5.10 ±0.84) mmol/L,t =3.727,P ＜0.01].However,Plasma levels of ET-1,TAT and hs-CRP in SCFS were higher than that of no SCFS [(94.3 ± 16.78) ng/Lvs (83.5±12.53) ng/L,t =3.051,P ＜0.01;(12.96±3.24)μg/Lvs (8.76 ±2.64)μg/L,t =5.945,P ＜ 0.01 ; (2.48 ± 0.35) μg/L vs (1.38 ± 0.46) μg/L,t =11.259,P ＜ 0.01].Furthermore,Logistic regression analysis showed that ET-1,TAT and hs-CRP were risk factors for SCFS (OR ＞ 1.22).Conclusions Due to coronary endothelial dysfunction,endothelial inflammatory reaction,and activated coagulation function,slow coronary flow of coronary artery occurs.
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This study was aimed to construct the pharmacophore models of endothelins A receptor antagonist in the application of screening traditional Chinese medicine (TCM) database for novel ETA Receptor antagonists. Qualitative and quantitative hypotheses were generated by HipHop and HypoGen separately on the basis of 36 compounds with antagonistic action on Endothelins A Receptor expressed in the aortic smooth muscle cells of rats. Database searching method was used to evaluate the generated hypotheses. The optimum hypotheses were used to search TCM database. The results showed that optimum qualitative hypothesis is with six features, which were one aromatic ring, one hydrogen-bond acceptors, one negative ionizable group and three hydrophobic groups, and the CAI value of 103.94. The optimum quantitative hypothesis is with six features, which were one aromatic ring, one hydrogen-bond acceptor, one negative ionizable group, two hydrophobic groups and one exclusive volume, and the CAI value of 45.96. Sixteen compounds from TCM were found in the database searching with the quantitative hy-pothesis. It was concluded that the pharmacophores are reliable and can be used to screen database for novel E-TA inhibitors. The qualitative and quantitative hypothesis can be used to screen database for active compounds and to predict the activity respectively.
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OBJECTIVES: Rheumatic fever is a highly prevalent disease in Brazil, and it poses a major public health problem. It is the leading cause of acquired heart disease in childhood and adolescence. The aim of this study was to evaluate the gene expression of ET-3 and its receptors, in replaced rheumatic mitral valves. METHODS: We studied the gene expression of endothelin-3 (ET-3) and its receptors, endothelin receptor A and endothelin receptor B (ETr-A and ETr-B), in the rheumatic mitral valves of 17 patients who underwent valve replacement surgery. The samples also underwent a histological analysis. RESULTS: Our data showed that almost all patients, regardless of individual characteristics such as gender or age, expressed the endothelin receptor genes, but did not express the genes for ET-3. In quantitative analysis, the ETr-A/GAPDH mean ratio was 33.04 ± 18.09%; while the ETr-B/GAPDH mean ratio was 114.58 ± 42.30%. Regarding histopathological individual features, the frequency of fibrosis is 100%, 88.23% of mononuclear infiltrate, 52.94% of neovascularization, 58.82% of calcification and absence of ossification. CONCLUSION: The presence of receptors ETr-A and ETr-B in rheumatic mitral valves suggests its interaction with the system of circulating endothelins, particularly ETr-B (known for acting in the removal of excess endothelin) detected in a greater proportion, which could explain the lack of expression of endothelin in rheumatic mitral valve, process to be elucidated.
OBJETIVOS: A febre reumática é uma doença altamente prevalente no Brasil, e representa um importante problema de saúde pública. É a principal causa de cardiopatia adquirida na infância e adolescência. O objetivo deste estudo foi avaliar a expressão gênica de ET-3 e seus receptores, em valvas mitrais reumáticas substituídas. Métodos: Estudamos a expressão gênica de endotelina-3 (ET-3) e de seus receptores, receptor da endotelina A e receptor da endotelina B (ETr-A e ETr-B), nas valvas mitrais reumáticas de 17 pacientes que se submeteram à cirurgia de troca valvar. As amostras também foram submetidas à análise histológica. RESULTADOS: Nossos dados mostraram que praticamente todos os pacientes, independentemente de características individuais, como sexo ou idade, expressaram os genes de receptores de endotelina, porém não expressaram os genes para ET-3. Na análise quantitativa, a média da proporção ETr-A/GAPDH foi de 33,04 ± 18,09%; enquanto que a média da proporção ETr-B/GAPDH foi de 114,58 ± 42,30%. Em relação às características histopatológicas individuais, a frequência de fibrose foi de 100%, infiltrado mononuclear de 88,23%, neovascularização de 52,94%, calcificação de 58,82% e houve ausência de ossificação. CONCLUSÃO: A presença de receptores ETr-A e ETr-B em valvas mitrais reumáticas sugere sua interação com o sistema de endotelinas circulantes, particularmente ETr-B (reconhecido por atuar na remoção do excesso de endotelina), detectado em maior proporção, o que poderia explicar a ausência da expressão de endotelina em valva mitral reumática, processo a ser elucidado.
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Adult , Female , Humans , Male , /genetics , Gene Expression/genetics , Mitral Valve Stenosis/genetics , Receptor, Endothelin A/genetics , Receptor, Endothelin B/genetics , Rheumatic Heart Disease/genetics , /metabolism , Heart Valve Prosthesis Implantation , Mitral Valve Stenosis/surgery , Receptor, Endothelin A/metabolism , Receptor, Endothelin B/metabolism , Rheumatic Heart Disease/metabolism , Rheumatic Heart Disease/surgeryABSTRACT
Background & objectives: Nutritional compounds which display anti-inflammatory and antioxidant effects have specific applications in preventing oxidative stress and endothelial dysfunction. In this study we evaluated the effect of Lisosan G (powder of Triticum sativum grains) on human microvascular endothelial cells (HMEC-1) exposed to oxidized low density lipoprotein (ox-LDL). Methods: The protective effects of Lisosan G were evaluated on human microvascular endothelial cells exposed to ox-LDL. Intercellular adhesion molecular-1 (ICAM-1), endothelin-1 (ET-1), and interleukin-6 (IL-6) concentrations and the expression of the respective genes were evaluated in response to incubation with ox-LDL, after co-incubation with ox-LDL and Lisosan G or exposed to Lisosan G alone. The analysis of LOX-1 gene was performed with RT-PCR semi quantitative method. The degree of oxidation induced in relation to control, was established by measurement of malondialdehyde (MDA) production. Results: The incubation with ox-LDL induced a significant increase in ICAM-1, IL-6 and ET-1 levels compared to the basal condition (P<0.01, P<0.05, and P<0.01, respectively), while in presence of Lisosan G, ICAM-1 levels showed a significant reduction both compared to the cultures treated with ox-LDL and control (P<0.01). IL-6 levels did not show any difference; ET-1 levels showed a partial reduction after co-treatment with Lisosan G, and also with Lisosan G alone, reduced the concentration below control (P<0.01). The modulation of these markers was confirmed by RT-PCR analysis. An association between MDA formation and the three markers production was observed. Semi-quantitative analysis of LOX-1 gene expression showed a significant up-regulation only after ox-LDL exposure. Interpretation & conclusions: The results demonstrate that Lisosan G may have an important role in the prevention of microcirculatory dysfunction.
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Analysis of Variance , Biomarkers/metabolism , Cell Line , Endothelial Cells/drug effects , Endothelial Cells/physiology , Endothelin-1/metabolism , Humans , Intercellular Adhesion Molecule-1/metabolism , Interleukin-6/metabolism , Lipoproteins, LDL/metabolism , Microcirculation/drug effects , Microcirculation/physiology , Microvessels/cytology , Plant Extracts/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Scavenger Receptors, Class E/metabolismABSTRACT
ObjectiveThe present study aimed to determine whether or not dual paroxysm proliferator-activated receptor (PPAR) agonist,WY14643,improved the dysfunctioned vascular endothelium in hypertension by reducing endothelium-derived contracting factors ( EDCFs ),and to explore the molecular mechanism it was involved in.MethodsIsometric tension in isolated thoracic aortic rings of spontaneously hypertensive rats was recorded.Endothelium-dependent contractions evoked by acetylcholine in the presence of L NAME were reduced by fenofibrate.Cyclooxygenase 1 ( COX1 ) activities were determined by analyzing the peroxidase activity of cyclooxygenase colorimetrically by using ELISA kit.ResultsCompared to the control group,WY14643 significantly decreased the vasoconstriction in aorta of the SHR rats(P=0.014).PPARα antagonist MK866 enhanced the vascular contractility of SHR rats that were incubated with 10.0μmol/L WY14643( P=0.021 ).PPARΥ antagonist GW9662 did not significantly affect the vascular contractility of SHR rats that were incubated with 10.0 μmol/L WY14643( P=0.061 ).The levels of serum PGFlα(P=0.012),2α( P =0.019) and TXB2(P=0.023) in SHR rats incubated with 10.0 μmol/L WY14643 were significantly lower than the control group,respectively.Under the condition of the existence of vascular endothelium,the expression of COX-1 in SHR rats incubated with WY14643 was significantly lower than that in SHR rats incubated without WY14643 (P=0.017).ConclusionsThose data showed that WY14643 reduced the release of EDCFs,it suggests that WY14643 protects against vascular diseases through the PPAR activators in spontaneous hypertension.
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BACKGROUND: The present study aimed to determine the changes of endothelin (ET), nitric oxide, and atrial natriuretic peptide (ANP) systems in the kidney and aorta in angiotensin (Ang) II-induced hypertension. METHODS: Male Sprague-Dawley rats were used. Ang II (100 ng.min-1.kg-1) was infused through entire time course. Fourteen days after beginning the regimen, aorta and kidney were taken. The protein expression of nitroc oxide synthase (NOS) was determined by semiquantitative immunoblotting. The mRNA expression of components of ET, NOS, ANP system was determined by real-time polymerase chain reaction. RESULTS: Hypertension was developed in the experimental group. mRNA expression of ET-1 in the aorta and kidney was increased. The protein expression of endothelial NOS (eNOS) was decreased in the aorta, while that of inducible NOS and neuronal NOS remained unaltered. mRNA expression of ANP, natriuretic peptide type (NPR)-A, and NPR-C was not changed in the aorta. CONCLUSIONS: Based on these results, it seems that in Ang II-induced hypertensive rats, increased expression of ET-1 in the aorta and kidney, and decreased eNOS expression in the aorta contribute to the pathogenesis of hypertension.
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Animals , Humans , Male , Rats , Angiotensin II , Angiotensins , Aorta , Atrial Natriuretic Factor , Endothelins , Hypertension , Immunoblotting , Kidney , Neurons , Nitric Oxide , Rats, Sprague-Dawley , RNA, MessengerABSTRACT
Objective To investigate the effect of repeated and prolonged +Gz exposure on endocrine function of vessel in a rabbit model of atherosclerosis. Methods Twenty-four male New Zealand white rabbits were used to establish the model of atherosclerosis, and then randomly divided into control group and +Gz exposure group (12 each). Animals in control group underwent no +Gz exposure, while those in +Gz exposure group underwent +Gz exposure for 4, 8, and 12 weeks respectively (4 animals at each time point), and 4 animals from each group were sacrificed at each time point. The levels of angiotensin II (Ang II), endothelin (ET), heme oxygenase-1 (HO-1), carbon monoxide (CO) and cyclic guanosine-3', 5'-monophosphate (cGMP) were measured by radioimmunoassay and biochemical method, and the ultrastructure of aortic intima was examined by electron microscopy. Results Along with the prolongation of +Gz exposure, the contents of Ang II, ET, HO-1, CO and cGMP were increased in +Gz exposure group (P<0.05), but the increase stopped at the 12th week, and no obvious change in the above indices was observed in control group (P=0.05). The foam cells and collagen content under the aortic intima and in the shallow layer of aortic media were slightly increased in control group, but the foam cells and the interstitial collagen fibers were greatly increased after +Gz exposure for 8 and 12 weeks as compared with that in control group. Conclusion Repeated and prolonged +Gz exposure may induce the production of Ang II and ET, increase the secretion of HO-1, CO and cGMP, thus play a potential role in protecting the vessels from further injuries.
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Objective To investigate the effect of repeated and prolonged +Gz exposure on endocrine function of vessel in a rabbit model of atherosclerosis. Methods Twenty-four male New Zealand white rabbits were used to establish the model of atherosclerosis, and then randomly divided into control group and +Gz exposure group (12 each). Animals in control group underwent no +Gz exposure, while those in +Gz exposure group underwent +Gz exposure for 4, 8, and 12 weeks respectively (4 animals at each time point), and 4 animals from each group were sacrificed at each time point. The levels of angiotensin II (Ang II), endothelin (ET), heme oxygenase-1 (HO-1), carbon monoxide (CO) and cyclic guanosine-3', 5'-monophosphate (cGMP) were measured by radioimmunoassay and biochemical method, and the ultrastructure of aortic intima was examined by electron microscopy. Results Along with the prolongation of +Gz exposure, the contents of Ang II, ET, HO-1, CO and cGMP were increased in +Gz exposure group (P<0.05), but the increase stopped at the 12th week, and no obvious change in the above indices was observed in control group (P=0.05). The foam cells and collagen content under the aortic intima and in the shallow layer of aortic media were slightly increased in control group, but the foam cells and the interstitial collagen fibers were greatly increased after +Gz exposure for 8 and 12 weeks as compared with that in control group. Conclusion Repeated and prolonged +Gz exposure may induce the production of Ang II and ET, increase the secretion of HO-1, CO and cGMP, thus play a potential role in protecting the vessels from further injuries.