Involvement of ET-1/eNOS in the ameliorating effect of electroacupuncture on cardiac dysfunction in rats with spontaneously hypertensive / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on cardiac function of ventriculus sinister in rats with spontaneously hypertensive (SHR), and to explore the mediation effect of endothelin-1 (ET-1)/endothelial nitric oxide synthase (eNOS).@*METHODS@#Six 12-week-old male Wistar Kyoto (WKY) rats were taken as the normal group. Eighteen 12-week-old SHR were randomly divided into a model group, an EA group and a sham EA group, 6 rats in each group. The rats in the EA group were treated with EA (disperse-dense wave, 2 Hz/15 Hz in frequency, 1 mA in current intensity) at "Neiguan" (PC 6), 30 min each time, once a day for 8 weeks. The rats in the sham EA group were treated with superficial needling at "Neiguan" (PC 6) with no electrical stimulation applied. After treatment, the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were tested by echocardiographic analysis. The left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), heart rate (HR), the maximum rate of increase/decrease of left ventricular pressure (±dp/dtmax) were detected. The serum content of ET-1 was detected by ELISA. Western blot was used to evaluate the expression of ETAR, eNOS in myocardial tissue of left ventricular.@*RESULTS@#Compared with the normal group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were decreased (P<0.01, P<0.05), while LVSP, LVEDP, +dp/dtmax and -dp/dtmax were increased (P<0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dtmax/LVSP and -dp/dtmax/LVSP were increased (P<0.01, P<0.05), and LVSP and LVEDP were decreased (P<0.01) in the EA group. Compared with the normal group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were increased (P<0.01), whereas expression of eNOS was decreased (P<0.01) in the model group. Compared with the model group, the serum content of ET-1 and the expression of ETAR in myocardial tissue were decreased (P<0.05), whereas expression of eNOS was increased (P<0.05) in the EA group.@*CONCLUSION@#EA intervention may alleviate hypertensive cardiac function damage by up-regulating the expression of eNOS protein in myocardial tissue, down-regulating the serum content of ET-1 and the expression of ETAR protein in myocardial tissue.

Effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome with different glucose tolerance status / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture on vascular endothelial function in patients of polycystic ovary syndrome (PCOS) with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT).@*METHODS@#A total of 140 patients with PCOS were divided into an IGT group (70 cases, 11 dropped off) and a NGT group (70 cases, 9 cases dropped off). The patients in the two groups were treated with full-cycle acupuncture at Zhongwan (CV 12), Guanyuan (CV 4), Qihai (CV 6), Tianshu (ST 25), etc. once every other day, 3 times a week, for 3 months. Before and after treatment, TCM symptom score, insulin resistance index [including fasting plasma glucose (FPG), 2-hour blood glucose (2hPG), fasting serum insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR)] and vascular endothelial related factors [including asymmetric dimethylarginine (ADMD), endothelin-1 (ET-1), malondialdehyde (MDA), nitric oxide (NO)] were compared between the two groups; in addition, the obese subgroup and non-obese subgroup of the two groups were further compared.@*RESULTS@#Compared before treatment, the TCM symptom scores, ADMD, ET-1 and MDA after treatment were decreased (@*CONCLUSION@#Acupuncture could improve vascular endothelial function in PCOS patients, IGT patients have better efficacy than NGT patients, and obese patients have better efficacy than non-obese patients.

Periodic Assessment of Antenatal and Post Natal Serum Endothelin-1 (ET-1) and Nitric Oxide (NO) Levels in Hypertensive Disorders of Pregnancy (HDP)

@#Introduction: Hypertensive Disorders of Pregnancy (HDP) is an independent risk factor of cardiovascular (CVS) disease with endothelial dysfunction postulated to be the pathophysiology. Endothelin-1 (ET-1), a potent vasoconstrictor, has been identified as a pivotal mediator in HDP. Disturbances in nitric oxide (NO) bioavailability found in endothelial dysfunction may increase susceptibility to cardiovascular diseases such as hypertension. The study aims to determine serial ET-1 and NO levels in patients with HDP and its role in persistent endothelial dysfunction. Materials and Methods: Thirty-six pregnant women from the following categories (i) normal pregnant women (Control) (ii) chronic hypertension during pregnancy (CH) and (iii) pregnancy induced hypertension (PIH) participated in this study. Blood pressure indices measurements and sample collection were done at antepartum (32 weeks) and postpartum (8 weeks and 12 weeks). ET-1 and serum NO were measured using the Human ET-1 (Endothelin-1) ELISA Kit and Nitric Oxide (total) detection kit respectively. Results: Serum ET-1 was significantly higher in patients with CH (55.3 pg/ml) and PIH (35.6 pg/ml) compared to Control (11.8 pg/ml) during antenatal until 3 months postpartum (CH 38.3 pg/ml, PIH 29.5 pg/ml, Control 1.9 pg/ml). This was accompanied by significantly lower levels of serum NO in HDP patients. Conclusion: Persistently higher than normal levels of ET-1 and lower than normal levels of NO up to 3 months postpartum in patients with history of HDP indicate presence of persistent endothelial dysfunction despite BP normalisation in PIH patients. Long term NO/ET-1 imbalance may account for the increased CVS disease risk.

Effect of Danggui Shaoyao San Drug-containing Serum on Expression of p-MLCⅡ and MLCⅡ Protein in HSC-T6 Cells Induced by ET-1 / 中国实验方剂学杂志

Objective:To investigate the effect of endothelin-1 (ET-1) on the expression of phosphorylated myosin light chain Ⅱ(p-MLCⅡ)and myosin light chain Ⅱ(MLCⅡ)protein in rat hepatic stellate cells HSC-T6 and explore the intervention effect of Danggui Shaoyao San(DSS)drug-containing serum. Method:After HSC-T6 cells were seeded, DMEM and blank rat serum with final concentrations of 2.5%, 5%, 10%, 15% and 20% were added to each well. The viability of HSC-T6 cells was determined by methyl thiazolyl tetrazolium(MTT) assay to screen the suitable serum concentration range. The cells were divided into blank serum control group (5%, 10%, 15%) and DSS drug-containing serum group (5%, 10%, 15%). ELISA was used to detect the content of ET-1 in cell culture supernatant under basic state. The cells were divided into blank serum control group (10%), DSS drug-containing serum low (5%), medium (10%) and high dose (15%) groups. Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) was used to detect the level of ET-1 mRNA in cell culture supernatant under basic state. The cells were divided into blank serum control group (10%), model group (10%), DSS drug-containing serum low (5%), medium (10%), high dose (15%) groups and Y-27632 inhibitor group (100 μmol·L-1). Except the blank serum control group, the other groups all received 10 nmol·L-1 ET-1 to induce HSC-T6 cells. Western blot was used to detect the expression of p-MLCⅡ and MLCⅡ in HSC-T6 cells induced by ET-1. Result:Serum concentrations of 5%, 10% and 15% were used as drug-containing serum concentrations. As compared with the blank serum control group, the DSS drug-containing serum group significantly reduced the relative content of ET-1 and ET-1 mRNA in the basic state (PPPPPConclusion:DSS drug-containing serum may down-regulate the expression of p-MLCⅡ and MLCⅡ by down-regulating the content of ET-1 and inhibiting the autocrine of ET-1.

Adjuvant treatment of acupoint catgut embedding for essential hypertension and its effects on vascular endothelial function / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of acupoint catgut embedding assisting western medication and simple western medication on blood pressure and vascular endothelial function in patients with essential hypertension (EH), and to explore its mechanism.</p><p><b>METHODS</b>A total of 125 cases were randomly assigned into an observation group (62 cases, 2 dropping) and a control group (63 cases, 3 dropping). Oral administration of lotensin (10 mg, once a day) was applied in the control group. Based on the treatment as the control group, acupoint catgut embedding was applied at Fengchi (GB 20), Ganshu (BL 18), Shenshu (BL 23), Quchi (LI 11), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) in the observation group, once every two weeks, and six treatments was taken as one session. All the patients were treated for 3 months. The blood pressure and the vascular endothelial injury markers, including endothelin-1 (ET-1), nitric oxide (NO), high sensitive C reactive protein (hsCRP) were recorded before and after treatment in the two groups. In addition, the ET-1, NO and hsCRP were collected from 60 cases of healthy participants.</p><p><b>RESULTS</b>The diastolic blood pressure and systolic blood pressure reduced after treatment in the two groups (all <0.05), which were more significant in the observation group (<0.01, <0.05). Before treatment, compared with those of the healthy participants, ET-1 and hsCRP were higher but NO was lower in the observation group and the control group (all <0.05); after treatment, ET-1 and hsCRP were reduced and NO increased in the two groups (all <0.05), which were more significant in the observation group (all <0.05). After treatment, the differences of NO and hsCRP between the observation group and healthy participants were not significant (both >0.05). The marked effective rate was 70.0% (42/60) in the observation group, which was superior to 33.3% (20/60) in the control group (<0.05); the total effective rate was 96.7% (58/60) in the observation group, which was superior to 85.0% (51/60) in the control group (<0.05).</p><p><b>CONCLUSION</b>The vascular endothelial function is injured in EH patients. Based on lotensin treatment, acupoint catgut embedding could significantly improve blood pressure and vascular endothelial function.</p>

cAMP induction by ouabain promotes endothelin-1 secretion via MAPK/ERK signaling in beating rabbit atria

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the Na(+)-K(+)-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain (3.0 micromol/L) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 (3.0 micromol/L), an inhibitor for reverse mode of Na(+)-Ca(2+) exchangers (NCX), but did not by L-type Ca2+ channel blocker nifedipine (1.0 micromol/L) or protein kinase A (PKA) selective inhibitor H-89 (3.0 micromol/L). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline (100.0 micromol/L), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP (0.5 micromol/L) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 (30 micromol/L), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

The changes of serum sialic acid in diabetic patients with chronic kidney disease and its relation with vascular endothelial function / 中国糖尿病杂志

Objective To observe the changes of serum sialic acid(SA)and in diabetic patients with chronic kidney disease(CKD) and its relation with vascular endothelial function. Methods 97 T2DM patients were divided into <30 mg/24 h group(n=31) ,30~299 mg/24 h group(n=34) and ≥300 mg/24 h group(n=32) according to the level of UAlb/Cr ,meanwhile 30 healthy subjects were selected as normal control(NC) group. The level of serum SA ,nitric oxide (NO) ,endothelin‐1(ET‐1) in four groups were detected. Results Compared with the NC group ,the level of SA and ET‐1 were increased gradually in <30 mg/24 h ,30 ~ 299 mg/24 h and ≥ 300 mg/24 h group ,and the NO were decreased gradually ( P<0.05) .Pearson correlation analysis showed that the SA level was positively related with ET‐1 and negatively with NO(P<0.05). Conclusion The level of SA is increased gradually in the development of CKD ,and the SA level is correlated with NO and ET‐1.

Effect of piperine for preventing on delayed cerebral vasospasm following experimental subarachnoid hemorrhage in rabbit / 基础医学与临床

Objective To observe whether piperine has the ability to prevent delayed cerebral vasospasm(DCVS) after subarachnoid hemorrhage(SAH).Methods Thirty-two New Zealand white rabbits were divided into four groups randomly(n=8).Group A(shamed-injecting blood): Puncture was completed without injecting blood into the cisterna magna;Group B(SAH): DCVS model was made with two-hemorrhage of SAH by injecting autologous arterial blood into the cisterna magna;Group C(SAH + piperine): Piperine(piperine(20 mg/kg),solvent(0.5 mL/kg)) was intravenously administrated daily since day 0 after first injection.Group D(SAH+DMSO): The solvent((0.5 mL/kg)) was gave by i.v.for DCVS models.All animals were sacrificed at day 7 after the first injection.The internal diameter and D/T(internal diameter/wall thickness) values of basilar artery(BA) were measured.The expression of ET-1 and eNOS in arterial wall of BA at day 7 was collected via immunohistochemistry method.Results The severe vasospasm of BA,over expression of ET-1 and diminished expression of eNOS in group B were found vs group A.The vasospasm of BA in group C was obviously alleviated in comparison with it in group B and D,respectively(P

Effect of Jiuqiang Naoliqing-containing serum on secretion of nitric oxide and endothelin-1 in human umbilical vein endothelial cells / 中国康复理论与实践

@#ObjectiveTo investigate the effect of Jiuqiang Naoliqing(JNQ)-containing serum on secretion of nitric oxide(NO) and endothelin-1(ET-1) in human umbilical vein endothelial cells(HUVECs), in order to explore the effect of JNQ on regulation of vascular active factors in HUVECs.MethodsThe HUVECs were explored to different volume fractions of JNQ containing serum after being isolated and cultured. The levels of cultured medium of NO and ET-1 were measured.ResultsThe cultured medium content of NO and ET-1 in different volume fractions of JNQ containing serum was significantly increased compared with normal serum control (P<0.05), while the ratio of NO to ET-1 were increased in comparison with normal control (P<0.05).Conclusion JNQ can be promoted secretion of NO and ET-1 in HUVECs, preserving endothelial function, and maintaining the balance of NO/E-1.

Pathophysiology of Persistent Pulmonary Hypertension of the Newborn / 소아과

Persistent pulmonary hypertension of the newborn(PPHN) is a disorder characterized by persistence of the pattern of fetal circulation after birth due to a sustained elevation of pulmonary vascular resistance. The two primary events in the pathophysiology of neonatal pulmonary hypertension are hypoxic pulmonary vasoconstriction(HPV) and hypoxic pulmonary vascular remodeling(HPR). Chronic hypoxemia may cause increased muscularity of the pulmonary arteries and extension of the muscularity to more distal arteries. The mechanisms underlying neonatal hypoxic pulmonary vascular remodeling are complex and multifactorial, requiring the involvement of endothelial, vascular smooth muscle, and adventitial cells. Endothelin-1(ET-1) has strong vasoactive properties, and acts via two different receptors, ETA and ETB. In pulmonary artery, ETA receptors mediate vasoconstriction and are found on vascular smooth muscle cells, while ETB receptors that are mostly located on endothelial cells mediate vasodilation by NO and prostacyclin release. eNOS derived NO is an important mediator of pulmonary vascular response to chronic hypoxia. Atrial natriuretic peptides(ANP) plays an important role in the regulation of pulmonary arterial pressure. Vascular endothelial growth factor (VEGF) release is increased in hypoxic pulmonary arterial smooth muscle cells, and hence may be involved in hypoxic pulmonary artery remodeling and edema. Retinol is essential for fetal lung morphogenesis and subsequent normal neonatal lung growth and maturation. ATP-sensitive potassium channels may be involved in the later stage of hypoxia. Activation of these channels may counteract the vasoconstrictive effect of hypoxia.

Clinical significance of endothelin-1 and P-selection in coronary heart disease / 中国康复理论与实践

@#ObjectiveTo explored the relationship among endothelin-1(ET-1), P-selection and troponin I(CTnI) in acute myocardial infarction (AMI) and unstable angina (UA).MethodsPlasma level of endothelin-1 was analyzed by radioimmunoassay, the expression of P-selection was analyzed by flow cytometery technique and troponin I was analyzed by paramagnetic partile chemiluminescent immunoassay in 23 AMI cases, 21 UA cases and 28 healthy controls.ResultsPlasma levels of ET-1 and CTnI in AMI patients were higher than in controls(P<0.05). The expression of P-selection in AMI patients was higher than in controls (P<0.01).Plasma levels of ET-1 and expression of P-selection in UA patients were higher than in controls (P<0.05). There was an increased trend of CTnI in UA patients in contrast to controls, but without statistical significance(P>0.05).As compared with UA, plasma levels of CTnI and expression of P-selection were elevated in AMI patients (P<0.05). No significant difference was observed between AMI and UA cases in plasma level of ET-1. Multivariate regression analysis revealed that P-selection was significantly associated with AMI and UA cases compared with plasma level of CTnI (r=0.404,P<0.01).ConclusionsPlasma levels of ET-1 and P-selection were sensitive markers as prethrombolic status.

Effect of pulse magnetic acupuncture apparatus on the nerve function and plasma endothelin-1 capacity of cerebral ischemia rat / 中国康复理论与实践

@#ObjectiveThe research is that pulse magnetic acupuncture in scalp point affects the nerve function and endothelin-1(ET-1)capacity of acute cerebral ischemia rat. Methods70 rats were divided randomly into seven groups: normal, artificial operation, model, static magnetic acupuncture, normal acupuncture, electric acupuncture and pulse magnetic acupuncture, every group had 10 rats and the nerve function and plasma ET-1 capacity of rats were examined.ResultsStatic acupuncture, electric acupuncture, pulse magnetic acupuncture and normal acupuncture can improve the nerve function and decrease the capacity of ET-1, but pulse magnetic acupuncture and normal acupuncture improve obviously.Conclusions Pulse magnetic acupuncture and normal acupuncture have the same effect to improve the nerve function and decrease the capacity of ET-1.

Effects of PSS on ET-1 secretion and platelet functions in the patients with early diabetic nephropathy / 中国海洋药物

Objective To investigate the effects and mechanism of action of PSS on the treatment of patients with early DN. Methods 76 patients with early DN were given PSS 100mg(iv gtt, qd) for 14 days. ET-1, TXB_2, 6-Keto-PGF_(1a), blood viscosity TG, TC, HDL-C, LDL-C and urine protein quantity(24h UPQ) were determined and compared between before and after treatment. Results All indexes above were improved significantly after therapy. Conclusion PSS may modulate ET-1 secretion and the ratio of TXB_2/6-Keto-PGF_(1a), reduce blood lipid content and viscosity, improve hemorrheology in patients with early DN.

Effects of Compound Xueniaoting metabolized by liver microsomeson glomerular mesangial cells / 中草药

Objective To study the mechanism of traditional Chinese medicine Compound Xueniaoting (CXNT) in treating glomerulus diseases with the main pathological changes of proliferation in mesangial cells. Methods CXNT and rat liver microsomes were incubated together, and then the incubated CXNT was added into cultured glomerular mesangial cells (GMC) in vitro. The proliferation of GMC was observed by MTT assay, the levels of interleukin-6 (IL-6) and endothelin-1 (ET-1) were determined by radioimmunoassay, and content of lactic dehydrogenase (LDH) was determined by velocity assay. ResultsCXNT (2, 4, 8 mg/mL) metobolized by rat liver microsomes could all inhibite the proliferation of GMC and production of IL-6 and ET-1 in a dose-dependent manner. Conclusion CXNT can inhibite the proliferation of GMC and restrain the secretion of IL-6 and ET-1, this function may be one of CXNT mechanisms in treating some mesangial proliferative glomerulonephritis.

Effect of Haikun Shenxi Capsule on Endothelin-1 and mRNA Expression in Kidney Tissue of Rats with Adriamycin-induced Nephrosis and Proliferation of Glomerular Mesanglal Cells / 中医杂志

Objective To study the effect of Haikun Shenxi Capsule(HSC)on endothelin-1(ET-1)and mRNA expression of rats with adriamyein-induced nephrosis and proliferation of glomerular mesangial cells(GMCs)cultured in vitro.Methods The rats were randomized into 6 groups,normal group,sham operation group,model group,benazepril group,HSC low-and high-dose groups.Ten weeks after treatment,ET-1 and mRNA expression were measured with immunohistochemical and hybridization in situ method.Tak- ing the Benazepril group as the control group,the proliferation of GMCs was detected with MTT method.Results In the model group,ET-1 and mRNA expression presented a strong positive,compared with which,that of the HSC low-and high-dose groups was remarkably reduced(P

Effects of Hirudo on level of Endothelin-1 in diabetic nephyropathy rats / 中成药

AIM:To study the effect of Hirudo on level of Endothelin-1(ET-1),kidney structure and function in diabetic nephyropathy(DN) rats. METHODS: STZ-induced DN rats were randomly divided into four groups: model group,Hirudo(17.5 g/kg,8.75 g/kg) treatment group,and captopril group,in addition,normal rats for control group.All rats were given by ig for 6 weeks.Kidney function and kidney index(kidney weight/body weight) were determined,the level of ET-1 was determined by Radioimmunoassay,the expression of ET-1 in the kidney tissue by immunohistochemicai,and kidney tissue was observed by lightmicroscope and transmission electron microscope. RESULTS: The level and expression of ET-1,kidney index in DN rats significantly increased.The level and expression of ET-1 markedly decreased in Hirudo treatment group,and kidney pathologic changes of DN rats in Hirudo treatment group were improved. CONCLUSION: Hirudo can ameliorate early kidney hyperdynamic abnormality in DN rats,possess protective effect on kidney of DN rats,whose mechanism may be associated partly with a down-regulation of levels and expression of ET-1.

Changes of ET-1 and TNF-? in dog ARF model during bilateral femoral arteriovenous shunt for extracorporeal membrane oxygenation / 西安交通大学学报(医学版)

Objective To study the changes of endothelin-1(ET-1) and tumor necrosis factor alpha(TNF?) in lung homogenate and plasm when acute respiratory failure(ARF) animal models are treated by bilateral femoral arteriovenous extracorporeal membrane oxygenation(bAV-ECMO).Methods Ten ARF dog models were treated by the bAV-ECMO.Right atrium blood and lung tissues were collected at different time points,and ET-1 and TNF? were assayed by radioimmunological method.Results ET-1 content in plasm decreased at first,and at 1h it was elevated and at 2h reached the peak.ET-1 content in lung homogenate reached the peak at 2h and then started to decrease.The analysis of variance showed notable differences(P