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To assess the effect of nesiritide on the endothelial function of iliac arteries following endothelia trauma. Right iliac artery trauma was created with a balloon catheter. Ten rabbits were treated with a 4-week subcutaneous injection of nesiritide at a fixed daily dose of 0.1mg/kg. Ten rabbits received daily normal saline injection. Plasma endothelin 1 (ET-1), nitric oxide (NO), and Von Willebrand Factor (vWF) were measured before and after the therapies. Tissue proliferating cell nuclear antigen (PCNA) was measured after the treatment. After the treatment, in the therapeutic group, the area under internal elastic membrane and the residual lumen area were higher than in the normal saline group (P <0.05). The plasma levels of ET-1 (91.6±6.8 vs 114.9±6.3 ng/L, P =0.001), vWF (134.6±10.8% vs 188.8±10.4%, P =0.001) and the ratio of PCNA positive expression (11.7±4.2% vs 36.2±11.4%, P =0.005) in the therapeutic group was lower than in the normal saline group, while the plasma levels of NO was higher (89.7±9.3 vs 43.5±5.3 µmol/L, P =0.001). Nesiritide inhibited remodeling of rabbit iliac artery following endothelial trauma. The inhibition of vascular remodeling may be related to the alleviated endothelial dysfunction and reduced expression of tissue proliferating cell nuclear antigen
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Animals , Male , Rabbits , Iliac Aneurysm/classification , Endothelin-1/adverse effects , Natriuretic Peptide, Brain/analysis , Endothelial Cells/drug effects , Wounds and Injuries/classification , von Willebrand Factor/analysis , Catheters/classification , Iliac Artery , Nitric Oxide/analysisABSTRACT
Objective To investigate the effect of oxygen glucose deprivation-reperfusion (OGD-R) in astrocytes overexpressing endothelin (ET)-1 on the proliferation of neural stem/progenitor cells (NSPCs). Methods OGD-R models of negative control astrocytes (C6-Mock) and astrocytes over-expressing ET-1 (C6-ET-1) were constructed. Transwell co-culture system of astrocytes and NSPCs was established. Morphologic observation and identification of the astrocytes and primary NSPCs were performed. The cells were divided into four groups: C6-Mock+NSPCs, OGD-R+C6-Mock+NSPCs, C6-ET-1+NSPCs and OGD-R+C6-ET-1+NSPCs groups and co-cultured for 0, 24, 48 and 72 h respectively. The diameter of neurosphere was measured in each group. Results In the C6-Mock and C6-ET-1 cells, type Ⅰ astrocytes in fibrous morphology were observed. Glial fibrillary acidic protein (GFAP) was expressed in the cytoplasm of these two types of cells. Primary NSPCs were positive for nestin staining. After co-culture for 48 and 72 h, the neurosphere diameter in the OGD-R+C6-Mock+NSPCs group was significantly greater than that in the C6-Mock+NSPCs group. The neurosphere diameter in the OGD-R+C6-ET-1+NSPCs group was considerably greater than that in the C6-ET-1+NSPCs group. The neurosphere diameter in the OGD-R+C6-ET-1+NSPCs group was significantly greater compared with that in the OGD-R+C6-Mock+NSPCs group (all P<0.05). Conclusions OGD-R astrocytes can promote the proliferation of NSPCs. ET-1 over-expression further accelerates the proliferation of NSPCs.
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Objective To study the correlation between coronary artery stenosis and endothelial dysfunction in patients with coronary heart disease and subclinical hypothyroidism.Methods According to the results of coronary angiography and thyroid function,the patients were divided into coronary heart disease with subclinical hypothyroidism (group A,n=71),coronary heart disease without subclinical hypothyroidism (group B,n=73), and normal coronary angiography (control group,n=59).The degree of coronary artery stenosis was evaluated by Gensini integral method.Fasting blood was taken to measure nitric oxide (NO),high sensitivity C reactive protein (hs-CRP),and endothelin (ET)to evaluate endothelial dysfunction.Results TC,TG,LDL-c,FT3,TSH,hs-CRP,ET and Gensini score were higher in Group A than in Group B and control group (P＜0.05).The level of NO in Group A and Group B were lower than that in control group (P＜0 .0 5).Multivariate Logistic regression analysis showed that age,TSH,ET and NO were independent risk factors for coronary heart disease.ET and NO levels in patients with coronary heart disease combined with subclinical hypothyroidism were correlated with Gensini scores (r=0.431,r=-0.383,P＜0.001).Conclusion Subclinical hypothyroidism may cause endothelial dysfunction in patients with coronary heart disease,which may increase cardiovascular risk in these patients.
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Objective To investigate the clinical effect of fasudil in heart failure induced by chronic pneumocardial disease and the influence in serum level of NO and ET-1.Methods 100 cases of patients with heart failure induced by chronic pneumocardial disease in our hospital from September 2013 to September 2016 were selected and divided into observation group and control group,50 cases in each group.Patients in the control group were treated with conventional therapy,and in the observation group were treated with fasudil based on the conventional therapy.Compared the clinical effect,blood oxygen partial pressure (PaO2),CO2 partial pressure (PaCO2),tricuspid regurgitation speed,fight ventricular outflow tract inside diameter(RVOT),left ventricular ejection fraction (LVEF) and serum biochemical indexes (NO and ET-1) levels.Results After treatment,the total effective rate of the observation group was significantly higher than control group (P ＜ 0.05).PaO2,LVEF,serum level of NO of the two groups were significantly higher,PaCO2,tricuspid regurgitation speed,RVOT,serum level of ET-1 significantly lower than before treatment (P ＜ 0.05),and the PaO2,LVEF,serum level of NO of observation group were significantly higher,PaCO2,tricuspid regurgitation speed,RVOT,serum level of ET-1 of observation group were significantly lower than control group (P ＜ 0.05).Conclusion Fasudil had remarkable clinical effect in heart failure induced by chronic pneumocardial disease,and improve the patient's clinical symptoms,adjust the serum level of NO and ET-1.
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@# ObjectiveTo study the relationship between Human Cytomegalovirus (HCMV) infection and endothelial function disorder and its possible role in nonspecific low back pain (NLBP).MethodsHCMV-DNA, -IgM, -IgG, HE stain, endothelin (ET) were detected in 50 patients with NLBP and 36 healthy people without NLBP(non-NLBP group).ResultsThe positive rate of HCMV-DNA,-IgM,-IgG, HE stain were higher in NLBP group than that in non-NLBP group(P<0.05), as well as the levels of ET(P<0.05).ConclusionHCMV infection may relate with NLBP, and ET may play an important role in it.
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OBJECTIVE:To observe the effect of Bilobalide on ischemical reperfusion injury in orthotopic liver transplantation model rats and to discuss its protective effect on ischemical reperfusion injury of rats undergoing liver transplantation.METHODS:The model of orthotopic liver transplantation was established by in rats by setting up the bridge between portal vein and left renal vein and building blood bypass by inlaying of canal in the inferior vena,after modeling,the rats were treated with Bilobalide,then levels of NO(active medium of blood vessel)and ET1 before ischemia and at 10 min,30min and 2h after reperfusion were determined by nitratase reduction method;serum levels of ALT,AST,ALP,LDH enzymology,ATP and MDA in the liver tissues were determined as well.The hepatic tissue sample was taken at 2h and fixed with formalin to be made into specimen for observation of the ultrastructure of liver cells and hepatic lobules under electron microscope.RESULTS:After being treated by Bilobalide,serum NO level was elevated and the pathological elevated levels of ALT,AST and LDH were brought down,the microcirculation in ischemical reperfusion injury rats was improved and the extent of damage in the ultrastructure of liver cells was lessened in rats.CONCLUSION:Bypass of portal vein and inferior vena cava prior liver transplantation is helpful for the prevention of ischemical reperfusion injury of liver.The balance of NO/ET1 is possibly a factor influencing the blood flow in the microcirculation of transplanted liver.Bilobalide was proved to be of protective effect on ischemical reperfusion injury in rats.
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@#ObjectiveTo observe the effect of Yiqihuoxue recipe on left ventricular remodeling after acute myocardial infarction (AMI).Methods40 patients with AMI were randomly divided into treatment group and control group with 20 cases in each group and received Yiqihuoxue recipe or fasinopril respectively for 6 months. Changes of clinical symptoms, the level of plasma angiotensin Ⅱ(ATⅡ), aldosterone (ALD), endothelin (ET) and echocardiographical indexes: left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), ejection fraction (EF), left ventricular mass index (LvmassI), wall motion index (WMI), wall thick (WT), E/A were assessed before discharge, and in the end of 3rd and 6th month after AMI.ResultsClinical symptoms of patients of treatment group improved significantly (P<0.01). EF and E/A of all patients in two groups increased (P<0.01 or P<0.05), LvmassI and WT reduced (P<0.05), but there were no significantly differences between two groups in LVEDVI, LVESVI, EF, LvmassI, WMI, E/A and WT(P>0.05). The level of plasma ET decreased in treatment group (P<0.05), the level of plasma ATⅡ and ALD of control group decreased more than that of treatment group (P<0.05).ConclusionYiqihuoxue recipe can significantly improve clinical symptoms, cardic function, and left ventricular remodeling, showing a better clinical efficacy.
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@#ObjectiveTo investigate the effect of scalp point penetration combined with rehabilitation training on content of endothelin (ET) and calcitonin gene-related peptide (CGRP) in plasma of patients with acute cerebral hemorrage (ACH).Methods90 ACH patients were randomly divided into the scalp point penetration combined with rehabilitation group (group A), the rehabilitation group (group B) and control group (group C) with 30 cases in each group. The radioimmunoassay was adopted to determinate the content of ET and CGRP in plasma of patients.ResultsAfter treatment, contents of ET and CGRP of all patients were decreased significantly (P<0.01), but group A and group B had a significant difference compared with the group C (P<0.01), and there was also a significant difference between the group A and group B.ConclusionThe scalp point penetration combined with rehabilitation training can regulate the content of ET and CGRP in plasma and make them under a dynamic balance.
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@#ObjectiveTo investigate the mechanism on endothelial dysfunction of spontaneous hypertensive rats (SHR).MethodsThe animals were divided into two groups: SHRs (n=8) and Wistar-Kyoto (WKY) rats (n=7) all aged 17 months. Blood pressure was measured by the tail-cuff method. NO3- concentration in serum was assayed by activated cadmium reduction method; endothelin (ET) and cGMP levels were assayed by RIA.ResultsCompared with WKY rats, blood NO3- concentration, ET level and vascular cGMP level of SHRs were all reduced significantly (P<0.01); vascular ET level was only uplifted slightly with no significant difference (P>0.05).ConclusionIt indicates that the vascular endothelial dysfunction in SHR is induced possibly by a diminished synthesis or release of NO, not by changes of ET level.
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Objective To investigate the effects of Stichopus variegatus mucopolysaccharide on plasma nitric oxide (NO) and serum endothelin(ET) after angioplasty in rabbits. Methods 50 New Zealand rabbits were randomly divided into four groups: Stichopus group, simvastatin group, model group and normal group. Endothelium of iliac arteries in Stichopus group, simvastatin group and model group were denuded by balloon catheter and the rabbits were fed with 2%cholesterol, 3%lard and 3%yolk mixed forage for six weeks, and then, atherosclerotic stenosis was showed by iliac angiography.When transluminal balloon angioplasty was done, from then on the feeds was changed from high cholesterol to ordinary forage. Stichopus (0.5g?kg -1?d -1) and simvastatin (0.5mg?kg -1?d -1) were given by gastric canal. While NaCl solution (0.9%) was given in model group. All rabbits were fed in separate cages and free drinking. After four weeks since transluminal balloon angioplasty, blood was collected from carotid artery to measure the changes of concentrations of endothelin(ET) and nitric oxide(NO). Examination of pathology by optical and electron microscope were done at same time. Results After four weeks since transluminal angioplasty, the concentration of plasm ET in model group increased significantly compared with the normal group(114.86?24.89 ng?L -1 vs 75.62?9.68 ng?L -1) and serum NO decreased significantly(37.50? 12.79?mol?L -1 vs 106.37?18.01 ?mol?L -1).The concentration of plasm ET in model group was higher than that in the simvastatin groups and Stichopus groups(114.86?24.89 ng?L -1 , 81.08?14.71 ng?L -1 and 83.34?11.41 ng?L -1 ,respectively),and the concentration of serum NO decreased obviously(95.63?8.62 ?mol?L -1,98.80?9.06 ?mol?L -1 and 37.50?12.79 ?mol?L -1,respectively). Conclusion After iliac arterial TA the concentrations of plasm ET were increased and the serum NO were decreased, the endothelial function fell into disorder. The Stichopus variegatus mucopolysaccharide had the effects of improving the endothelial function after angioplasty in rabbits by adjustment of plasm ET and serum NO.
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BACKGROUND: Sepsis is a clinical syndrome characterized by a systemic inflammatory and hemodynamic response to severe bacterial infections that involve various mediators. Endothelin (ET)-1, a potent vasocon strictor is associated with multiple organ failure, and interleukin (IL)-8, a proinflammtory cytokine, plays a major role in neurophil activation. Both have been reported to be useful parameters in the clinical assessment of sepsis. The levels of ET-1 and IL-8 in the blood were measured in patients with sepsis, and the correlation of both parameters and their relationship with the clinical data was assessed. METHODS: 19 sepsis patients and 17 controls were studied. Blood samples of the sepsis patients were drawn in day 1, 3, 7, and 14. the APACHE III scores were calculated in concurrent days. The ET-1 and IL-8 levels were measured using immunoassay methods. RESULTS: The ET-1 levels of patients with sepsis were significantly higher than in the controls. In patients with sepsis, non-survivors had higher ET-1 levels than survivors on day 1 and 7, and patients with shock also had higher ET-1 levels than normotensive patients on admission. The ET-1 levels were significantly correlated wit the creatinine levels in day 1, 7, and 14. The IL-8 levels showed a significant correlation with the ET-1 levels on day 14. CONCLUSION: ET-1 was found to be closely related with the clinical outcome, shock, and renal failure, and showed a correlation with IL-8. these mediators can be considered not only to play pathophysiologic roles but also as useful parameters in the clinical assessment of sepsis.
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Humans , APACHE , Bacterial Infections , Creatinine , Endothelin-1 , Endothelins , Hemodynamics , Immunoassay , Interleukin-8 , Interleukins , Multiple Organ Failure , Naphazoline , Renal Insufficiency , Sepsis , Shock , SurvivorsABSTRACT
BACKGROUND: The purpose of this study was to investigate the mechanism of endothelium-dependent and independent responses to endothelins (ETs) in porcine coronary artery. METHODS: The vascular rings of left anterior descending artery or left circumflex artery from 7 pigs were suspended in conventional organ chambers for the measurement of isometric force. To evaluate relaxation responses, vascular rings with endothelium were exposed to ET-1 and ET-3. To evaluate contraction responses, vascular rings with and without endothelium were exposed to ET-1 and ET-3 in the presence or absence of BQ 123 (ET(A) receptor antagonist) or TAK-044 (ET(A) and ET(B) receptor antagonist). RESULTS: Transient relaxation responses of vascular rings occurred after exposure of ET-1 and ET-3. These transient responses disappeared after preincubation with N-nitro-L arginine. There was an increased contractions of vascular rings according to increasing concentration of ET-1 and ET-3. The initial responses were enhanced in vascular rings without endothelium in ET-1 and ET-3. In vascular rings with endothelium, the contraction responses were more reduced in vascular rings with preincubation of BQ 123 than in vascular rings without BQ 123 in ET-1. In vascular rings without endothelium, the contraction responses were more reduced in vascular rings with preincubation of TAK-044 than in vascular rings without TAK-044 in ET-1. CONCLUSION: ET(B) receptor on the endothelium might mediate the transient vasodilator responses to ET-1 and ET-3 through release of nitric oxide in porcine coronary artery. ET(A) and ET(B) receptor on vascular smooth muscle cells might mediate vasoconstrictor responses to ETs.
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Arginine , Arteries , Coronary Vessels , Endothelins , Endothelium , Muscle, Smooth, Vascular , Nitric Oxide , Receptors, Endothelin , Relaxation , SwineABSTRACT
The antihypertensive effect of marine sulfated polysaccharide AHD and its underlying mechanisms were studied in renovascular hypertensive rats (RHR) [two-kidney one clip,Goldblatt(2-K 1C)J. AHD were given orally at doses of 12.5, 25,50mg?kg～-1 once a day for five weeks,simultaneously wity the initiation of the establishment of renovascular hypertensive model. Serum nitric oxide(NO) was determined with NO kit,and plasma Angiotensin E (Ang Ⅱ ) and Eneothelin (ET) Were measured by radioimmumoassays. The results indicated that AHD decreased arteial blood pressure in a dose-dependent manner. Moreover, nitric oxide (NO) contents in serum were dose-dependently elevated,accompanied by dramatic reduction in Ang Ⅱ and ET contents. These findings suggested that AHD exerted its hypotensive activity by enhancing tye release of NO,followed by reduction in production of boty ANG Ⅱ and ET in vivo.
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Object To probe into the antihypertension activity mechanism of extracts from Compound Jueming (CJ). Methods The method of radioimmunoassay was used to assay the concentration of the related substances on spontaneously hypertensive rats (SHR) such as angiotensin Ⅱ (ANGⅡ), renin activity (RA), endothelin (ET), atrial natriuretic polypeptide (ANP), aldosterone (ALD), and urine. Results All of the three doses (9.5, 7.2, and 4.8 g/kg) of extracts from CJ reduced ANG Ⅱ and RA, but had no influence on ALD, ET, ANP, and urine in SHR. Conclusion The antihypertension effect of extracts from CJ is related to decreasing of renin angiotensin, but not to ALD, ET, ANP, and urine.
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Objective To evaluate the effects of Yangxue Qingnao Granules (YQG) in decreasing blood pressure in rats with renal hypertension and to investigate its mechanism.Methods Modified Goldblatt renal hypertension rat models were used.The rats were randomized into 6 groups: model group,YQG groups (treated with high-,moderate-and low-dose respectively),Captopril Tablets group and Niuhuang Jiangya Pills group, 10 rats in each group. The model group was given with distilled water and the other groups with corresponding drugs by gavage, once time a day. Blood pressure was detected in 1st, 2nd and 4th week after treatment. Four weeks after treatment plasma levels of endothelin (ET),calcitonin gene related peptide(CGRP) and nitric oxide(NO) were examined by radioimmunoassay.Results Plasma level of ET was increased and those of NO and CGRP were decreased in rats with renal hypertension. YQG could decrease ET level and increase the levels of NO and CGRP, high-dose YQG in particular (P
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Objective To study the effect and its mechanism of Modified Wenjing Decoction(Decoction for warming channels)on vasomotion in patients with menstrual disease of blood stasis due to cold accumulation.Methods The 50 patients of emmeniopathy with blood stasis due to cold accumulation were successively treated with Modified Wenjing Decoction for three menstrual cycles.The therapeutic effect and changes of nitrous oxide(NO),endothelin(ET),thromboxane B2(TXB2),6 ketone prostaglandin F1?(6-keto-PGF1?)of menstrual blood,reproductive hormones estradiol(E2)and progesterone(P)before and after treatment were observed.Results Of the 50 patients,19(38.0%)were short-term cured,24(48.0%)effective,and 7(14.0%)ineffective.After treatment,the levels of menstrual blood ET and TXB2 were decreased significantly(P
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0.05). The serum levels of E_2 in patient group were significantly lower than those of the regular menses group (P0.05). The serum levels of E_2 were significantly higher in patient group after treatment (P0.05). The menstrual blood levels of NO, E_2 were significantly higher, and ET were significantly higher, respectively, in patient group after treatment (P
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Endothelin (ET), recently isolated from culture supernatant of porcine aortic endothelial cells, is a novel potent vasoconstrictive substance. In this paper a highly specific rabbit antisera against endothelin was used to study the localization of ET in the isolated endothelial cells, from human umbilical veins and porcine arota, and that of ET in the cryostat cross sections of porcine aorta by using ABC immunohistochemical technique. The results demonstrate that a varied amounts of specific ET-like immunoreactive substance exist in the endothelial cytoplasm of human umbilical veins and porcine aorta which provides the mor- phological evidence for elucidating the endocrine function of vascular endothelial cells.
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By means of 3H-Thymidine and3H-Leucine incorporation, we observed that CGRP inhibited the multiplication of SHR's aortic smooth muscle cells (VSMCs) and the proliferation of VSMCs stimulated by Endothelin. These results suggest that CGRP may be a natu-ral antagonist of Endothelin in human body.