Objective To investigate the role of the endothelin-1/nitric oxide （ET-1/NO） system in neurological function and cerebral hemodynamics after interventional surgery for cerebral infarction， as well as the association of the levels of ET-1 and NO with neurological recovery and cerebral blood flow after surgery. Methods A total of 108 patients with cerebral infarction who were treated in our hospital from January 2022 to June 2023 were enrolled， and serum samples were collected before surgery and on day 30 after surgery. ELISA was used to measure the levels of ET-1 and NO；National Institutes of Health Stroke Scale（NIHSS） was used to assess neurological function； transcranial Doppler was used to measure cerebral hemodynamic parameters， including mean blood flow velocity， peak systolic velocity， and pulsatility index. A Spearman correlation analysis was used to investigate the correlation of ET-1 and NO with neurological function and cerebral hemodynamics，and the receiver operating characteristic （ROC） curve was used to assess the value of ET-1 and NO in predicting poor neurological function. Results After interventional surgery， there was a significant reduction in the level of ET-1 and a significant increase in the level of NO（both P<0.001）. The patients were divided into good recovery group （NIHSS≤5） and poor recovery group.Compared with the poor recovery group， the good recovery group had a significant reduction in serum ET-1 and a significant increase in serum NO （both P<0.001）. The Spearman correlation analysis showed that the serum level of ET-1 was negatively correlated with neurological recovery and the improvement in cerebral hemodynamics， while the level of NO was positively correlated with these two indicators. The ROC curve analysis showed that ET-1 and NO could effectively predict poor neurological recovery after interventional surgery， with an area under the ROC curve of 0.881 and 0.981，respectively. Conclusion The ET-1/NO system plays an important role in neurological function and cerebral hemodynamics after interventional surgery for cerebral infarction. Reducing ET-1 and increasing NO can facilitate the recovery of neurological function and cerebral blood flow after surgery. The levels of ET-1 and NO can be used as biomarkers for predicting poor postoperative neurological function and provide a scientific basis for optimizing postoperative treatment strategies.
Endothelin-1

Endothelin-1 is a peptide derived from endothelial cells, consisting of 21 amino acid residues. In recent years, research has found that endothelin-1 not only plays a key role in vascular tone regulation but also participates in the occurrence and development of various types of pathological pain, including inflammatory pain, neuropathic pain, and cancer pain. Endothelin-1 binds to its receptors and activates multiple signaling pathways such as protein kinase C, calcium ion channels, and the phosphoinositide pathway, thereby influencing neuronal excitability and nociceptive information transmission. This article briefly reviews the current understanding of the mechanisms and potential roles of endothelin-1 in the development of pain, as well as commonly used endothelin-1 receptor antagonists, aiming to provide clues for better utilizing endothelin-1 and its receptors to alleviate and treat pathological pain.
Humans ; Endothelin-1/physiology* ; Pain/physiopathology* ; Signal Transduction/physiology* ; Animals ; Neuralgia/physiopathology* ; Cancer Pain/physiopathology* ; Endothelin Receptor Antagonists

OBJECTIVES: To study the association between hepatocyte growth factor (HGF) and treatment response in mice with hypoxic pulmonary arterial hypertension (HPAH) and the possibility of HGF as a new targeted drug for HPAH. METHODS: After successful modeling, the HPAH model mice were randomly divided into two groups: HPAH group and HGF treatment group (tail vein injection of recombinant mouse HGF 1 mg/kg), with 10 mice in each group. Ten normal mice were used as the control group. After 5 weeks, echocardiography was used to measure tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio; the Griess method was used to measure the content of nitric oxide in serum; ELISA was used to measure the serum level of endothelin-1; transmission electron microscopy was used to observe changes in the ultrastructure of pulmonary artery. RESULTS: Compared with the HGF treatment and normal control groups, the HPAH group had significantly higher tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio (P<0.05). The transmission electron microscopy showed that the HPAH group had massive destruction of vascular endothelial cells and disordered arrangement of the elastic membrane of arteriolar intima with rupture and loss. The structure of vascular endothelial cells was almost complete and the structure of arterial intima elastic membrane was almost normal in the HGF treatment group. Compared with the normal control and HGF treatment groups, the HPAH group had significantly higher serum levels of nitric oxide and endothelin-1 (P<0.05). CONCLUSIONS Increasing serum HGF level can alleviate the impact of HPAH on the cardiovascular system of mice, possibly by repairing endothelial cell injury, improving vascular remodeling, and restoring the normal vasomotor function of pulmonary vessels.
Animals ; Body Weight ; Endothelial Cells ; Endothelin-1 ; Hepatocyte Growth Factor/therapeutic use* ; Hypertrophy, Right Ventricular ; Hypoxia ; Mice ; Nitric Oxide ; Pulmonary Arterial Hypertension/drug therapy*

OBJECTIVE: To investigate the changes in serum levels of endothelin-1 (ET-1) and connective tissue growth factor (CTGF) in patients with atrial fibrillation (AF) and their value for predicting recurrence of AF after radiofrequency ablation (RFCA). METHODS: Sixty-six patients with paroxysmal AF (PaAF) and 72 with persistent AF (PaAF) admitted in our hospital were recruited as AF group and 80 patients with sinus rhythm as the control group, and in all the participants, serum levels of ET-1 and CTGF were measured using ELISA and Western blotting. From 6 patients with AF and 6 with sinus rhythm undergoing cardiac surgery in our hospital, tissue samples of the right atrial appendage were taken intraoperatively for observation of structural changes of the cardiomyocytes, myocardial fibrosis and expression of ET-1 and CTGF protein. In AF group, the patients receiving RFCA were followed up for 6 months following the procedure for assessment of the outcomes. RESULTS: Compared with the control patients, the patients with AF showed obvious damages of the cardiomyocyte structure and myocardial fibrosis. Serum levels of ET-1 and CTGF levels were significantly higher in PaAF and PeAF groups than in the control group, and were higher in PeAF group than in PaAF group. In the patients with AF, serum ET-1 and CTGF levels were positively correlated with left atrial diameter (LAD) (P < 0.05), and ET-1 was positively correlated with CTGF levels (P < 0.05). In patients with postoperative AF recurrence, the serum levels of ET-1 and CTGF were significantly higher than those in patients without recurrence; serum ET-1 and CTGF levels before and after the operation were positively correlated with the recurrence of PeAF, and elevated serum levels of ET- 1 and CTGF were identified by logistic regression analysis as independent risk factors for postoperative recurrence of PeAF. CONCLUSION Serum levels of ET-1 and CTGF are significantly elevated in AF patients in positive correlation with AF duration. ET-1 and CTGF levels are higher in AF patients with postoperative recurrence, and they both have predictive value for recurrence of PeAF following RFCA.
Humans ; Atrial Fibrillation ; Endothelin-1 ; Connective Tissue Growth Factor ; Chronic Disease ; Atrial Appendage ; Fibrosis

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/dt_max) 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/dt_max/LVSP and -dp/dt_max/LVSP were decreased (P<0.01, P<0.05), while LVSP, LVEDP, +dp/dt_max and -dp/dt_max were increased (P<0.01) in the model group. Compared with the model group, LVEF, LVFS, +dp/dt_max/LVSP and -dp/dt_max/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.
Animals ; Electroacupuncture ; Endothelin-1/genetics* ; Heart Diseases ; Hypertension/therapy* ; Male ; Nitric Oxide Synthase Type III/genetics* ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Stroke Volume ; Ventricular Function, Left

PURPOSE: This study aimed to investigate the effect of adipose-derived stem cell (ADSC) transplantation on atherosclerosis (AS) and its underlying mechanisms. MATERIALS AND METHODS: In our study, rat AS model was established, and ADSCs were isolated and cultured. Atherosclerotic plaque and pathological symptoms of thoracic aorta were measured by Oil Red O staining and Hematoxylin-Eosin staining, respectively. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by an automatic biochemical analyzer. Expressions of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), aortic endothelin-1 (ET-1), interleukin-6 (IL-6), c-reactive protein (CRP), and tumor necrosis factor α (TNF-α) were measured by enzyme linked immunosorbent assay, VEGF, VCAM-1, ICAM-1, ET-1, respectively, and NF-κB p65 mRNA expressions were detected by quantitative real-time polymerase chain reaction. Protein expressions of VEGF, VCAM-1, ICAM-1, ET-1, NF-κB p65, p-NF-κB p65, and IκBα were measured by western blot. Moreover, NF-κB p65 expression was measured by immunofluorescence staining. RESULTS: ADSC transplantation alleviated the pathological symptoms of aortic AS. ADSC transplantation decreased the levels of TC, TG, and LDL-C and increased serum HDL-C level. Meanwhile, ADSC transplantation decreased the levels of IL-6, CRP, and TNF-α in AS rats. Moreover, the expressions of VEGF, ET-1, VCAM-1, and ICAM-1 were decreased by ADSC transplantation. ADSC transplantation inhibited phosphorylation of NF-κB p65 and promoted IκBα expression in AS rats. CONCLUSION: Our study demonstrated that ADSC transplantation could inhibit vascular inflammatory responses and endothelial dysfunction by suppressing NF-κB pathway in AS rats.
Animals ; Aorta, Thoracic ; Atherosclerosis ; Blotting, Western ; C-Reactive Protein ; Cholesterol ; Endothelin-1 ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Lipoproteins ; Phosphorylation ; Plaque, Atherosclerotic ; Rats ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Stem Cell Transplantation ; Stem Cells ; Triglycerides ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1 ; Vascular Endothelial Growth Factor A

OBJECTIVE: To investigate the vascular damage effects and possible mechanism of acute exposure to ozone (O) in male Wistar rats. METHODS: One hundred and twenty male Wistar rats were randomly divided into six groups, 20 in each group. The experimental animals were placed in a gas poisoning cabinet, the control group was exposed to filtered air, and the treatment group was exposed to ozone at concentrations of 0.12 ppm, 0.5 ppm, 1.0 ppm, 2.0 ppm, and 4.0 ppm, respectively, for 4 hours. Arterial blood pressure data were obtained by PC-lab medical physiological signal acquisition system. Blood rheology indicators and blood biochemical indicators were detected by Tianjin Dean Diagnostic Laboratory. Serum endothelin-1 (ET-1), homocysteine (HCY), von Willebrand factor (vWF), 8-hydroxydeoxyguanosine (8-OhdG), interleukin (IL-6) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) microplate assay. Oxidative stress indicators superoxide dismutase (SOD) activity and malondialdehyde (MDA) were determined by xanthine oxidase method, thiobarbituric acid (TBA) method, reduced glutathione (GSH) and nitric oxide (NO) were tested by using microplate colorimetry. Paraffin sections were prepared from thoracic aorta tissue, and vascular structure was observed by HE staining. RESULTS: Acute exposure to 0.12 ppm ozone could cause a significant increase in arterial systolic blood pressure (SBP). Exposure to different concentrations of ozone could cause a significant increase in plasma viscosity, and the K value of the ESR equation was significantly increased in the 1.0 ppm ozone exposure group. Both the relative and reduced viscosities were significantly reduced at ozone concentrations of 0.5 ppm and 4.0 ppm, while the red blood cell deformation index was increased significantly at ozone concentrations of 0.12 ppm, 0.5 ppm, 1.0 ppm, and 2.0 ppm. Acute ozone exposure resulted in the decrease of total cholesterol content. The content of high-density lipoprotein cholesterol (HDL-C) was significantly reduced in the 0.12 ppm ozone exposure group. When the ozone concentration was higher than 1.0 ppm, the body may also had an inflammatory reaction (increased TNF-α) and oxidative stress (increased MDA, decreased GSH). Acute exposure to ozone could lead to elevated levels of ET-1 in the blood, with significant differences in the 4.0 ppm concentration group, while HCY levels were decreased firstly and then increased, reaching the highest in the 1.0 ppm concentration group. No obvious pathological changes were observed in the thoracic aorta. CONCLUSION Acute ozone exposure can affect arterial blood pressure, blood rheology and cholesterol metabolism in rats. The possible mechanism is that ozone exposure leads to inflammatory reaction and oxidative stress reaction, causing vascular endothelial function damage, and vascular endothelial cells increase with ozone exposure concentration.
Animals ; Blood Vessels ; injuries ; Deoxyguanosine ; analogs & derivatives ; blood ; Endothelin-1 ; blood ; Homocysteine ; blood ; Interleukin-6 ; blood ; Male ; Malondialdehyde ; analysis ; Oxidative Stress ; Ozone ; toxicity ; Rats ; Rats, Wistar ; Superoxide Dismutase ; analysis ; Tumor Necrosis Factor-alpha ; blood ; von Willebrand Factor ; analysis

OBJECTIVETo evaluate the efficacy and safety of Tongxinluo Capsule (, TXL) for patients with cardiac syndrome X (CSX).

METHODSRandomized controlled trials (RCTs) regarding TXL in the treatment of CSX were searched in Chinese Biomedicine Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, PubMed, EMBASE, Cochrane Central Register of Controlled Trial, websites of the Chinese and International Clinical Trial Registry platform up to June 30, 2015. The intervention was either TXL alone or TXL combined with conventional treatment, while the control intervention was conventional treatment with or without placebo. Data extraction, methodological quality assessment and data analyses were performed according to the Cochrane criteria. The primary outcome was a composite event of death, acute myocardial infarction (AMI), angina requiring hospitalization, revascularization, and heart failure. The secondary outcome measures were angina symptom improvement, electrocardiograph (ECG) improvement, and serum endothelin-1 (ET-1) level. The adverse events were also recorded. RevMan 5.3 software was applied for data analyses.

RESULTSTwelve RCTs (696 patients) were included. Compared with conventional treatment, the addition of TXL to conventional treatment showed some benefits on relieving angina symptoms [risk ratio (RR): 1.46, 95% confidence interval (CI) (1.25, 1.71), P<0.01], and improving ECG [RR: 1.45, 95% CI (1.21, 1.74), P<0.01]. The pooled result did not support a benefit of TXL on reducing the incidence of primary outcome [RR: 0.20, 95% CI (0.02, 1.61), P=0.13]. In addition, TXL decreased serum ET-1 concentration of CSX patients [standardized mean number:-1.63, 95% CI (-2.29,-0.96), P<0.01]. No serious adverse events were reported.

CONCLUSIONSTXL documents potential benefits on attenuating angina symptoms, improving ECG and decreasing serum ET-1 level for CSX patients. However, more rigorous RCTs with high quality are needed to confirm its efficacy and safety.

Capsules ; Cardiovascular Diseases ; diagnostic imaging ; drug therapy ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Electrocardiography ; Endothelin-1 ; blood ; Humans ; Middle Aged ; Outcome Assessment (Health Care) ; Publication Bias ; Syndrome

This study aimed to investigate the antihypertensive effect and possible mechanism of Dendrobium officinale flos on hypertensive rats induced by high glucose and high fat compound alcohol. The hypertensive models were successfully made by high-glucose and high-fat diet, with gradient drinking for 4 weeks, and then divided into model control group, valsartan (5.7 mg·kg⁻¹) positive control group and D. officinale flos groups (3，1 g·kg⁻¹). After 6 weeks of treatment, the blood pressure of rats was measured regularly. After the last administration, endothelin-1 (ET-1), thromboxane B₂ (TXB₂), prostacyclin (PGI₂) and nitric oxide (NO) were tested. Endothelial nitric oxide synthase (eNOS) expression and lesion status in thoracic aorta were detected. The vascular endothelium dependent dilation of the thoracic aorta was detected by the isolated vascular loop tension test. The results showed that D. officinale flos could significantly reduce systolic blood pressure and mean arterial pressure in hypertensive rats, inhibit the thickening of thoracic aorta and the loss of endothelial cells, reduce plasma content of ET-1 and TXB₂, and increase the content of PGI₂ and NO. After long-term administration, vascular endothelium dependent dilation of the thoracic aorta was significantly increased, and could be blocked by the eNOS inhibitor (L-NAME) and increase the expression of eNOS. Therefore, D. officinale flos has an obvious antihypertensive effect on high glucose and high fat compound alcohol-induced hypertensive rats. Its mechanism may be correlated with the improvement of vascular diastolic function by protecting vascular endothelial cells, and finally resist hypertension.
Animals ; Antihypertensive Agents ; pharmacology ; Blood Pressure ; Dendrobium ; chemistry ; Diet, High-Fat ; Drugs, Chinese Herbal ; pharmacology ; Endothelin-1 ; blood ; Endothelium, Vascular ; drug effects ; Epoprostenol ; blood ; Glucose ; Hypertension ; chemically induced ; drug therapy ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; T-Box Domain Proteins ; blood ; Vasodilation

Neurofibromatosis type 1 (NF1) is a rare genetic disease. Precapillary pulmonary hypertension (PH) with NF1 is an extremely severe complication. A 65-year-old woman was admitted in our hospital with 3-year history of gradually worsening dyspnea on exertion (New York Heart Association functional class III-IV). Considering her clinical feature and examination findings, she could be diagnosed as PH associated with NF1. She was treated with endothelin receptor antagonist. However her dyspnea was not significantly improved. This is the first Korean case of NF1 patient with PH which confirmed with right heart catheterization.
Aged ; Cardiac Catheterization ; Cardiac Catheters ; Dyspnea ; Female ; Heart ; Humans ; Hydrogen-Ion Concentration ; Hypertension, Pulmonary* ; Neurofibromatoses* ; Neurofibromatosis 1* ; Receptors, Endothelin