OBJECTIVETo observe the effects of Danhong Injection (丹红注射液) and its main components, including daiclzein and hydroxysafflor yellow A (HSYA), on the anticoagulation, fibrinolysis, anti-apoptosis in hypoxia model of vein endothelial cells (VECs).

METHODSVECs were prepared and were put in a hypoxia environment, which consisted of mixed gas of 95% N and 5% CO mixed gas, when reached confluent culture. Five groups used different treatments, including normal control group, hypoxia group, daiclzein group, HSYA group and Danhong Injection group. The VECs were identified by fluorescence double labeling methods. The morphology was observed by a phase contrast microscopy. The effects of Danhong Injection, daiclzein and HSYA on 6 keto prostaglandin F1α (6-keto-PGF1α) level was measured by the method of radioimmunoassay (RIA). Superoxide dismutase (SOD) activity was tested by water soluble tetrazolium salt. The content of malondialdehyde (MDA) was measured by thiobarbituric acid. The activities of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were measured by the method of chromogenic substrate. The contents of endothelin (ET) and nitric oxide (NO) were detected by non-equilibrium RIA and enzymelinked immunosorbent assay. Cells apoptosis rate was determined by flow cytometry.

RESULTSCompared with the normal control group, the floating cells number, PAI activity, ET and MDA contents, and cells apoptosis rate in the culture solution of hypoxia group were all significantly increased, whereas the 6-keto-PGF1α and NO contents, and t-PA and SOD activities were decreased significantly (P<0.01). Compared with the hypoxia group, Danhong Injection markedly increased the 6-keto-PGF1α content and SOD activity, regulated PAI and t-PA activities, ET and NO contents, and decreased MDA content and cells apoptosis rate (P<0.05 or P<0.01).

CONCLUSIONSDanhong Injection and its main components played an important role in protecting primary VECs from hypoxic damage by regulating the secretion and vasomotor function of VECs. The function of Danhong Injection was most remarkable.

6-Ketoprostaglandin F1 alpha ; metabolism ; Animals ; Apoptosis ; drug effects ; Blood Coagulation ; drug effects ; Cell Count ; Cells, Cultured ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; Endothelins ; metabolism ; Factor VIII ; metabolism ; Fibrinolysis ; drug effects ; Fluorescent Antibody Technique ; Humans ; Infant, Newborn ; Injections ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Plasminogen Inactivators ; metabolism ; Rabbits ; Superoxide Dismutase ; metabolism ; Tissue Plasminogen Activator ; metabolism ; Umbilical Veins ; cytology

OBJECTIVE: To investigate the significance of tumor necrosis factor-alpha (TNF-α) and plasma endothelium (ET) in pathophysiologic process of patients with obstructive sleep apnea hypopnea syndrome(OSAHS) with type 2 diabetes mellitus (T2DM). METHOD: All observed subjects were divided into 4 groups. A number of 80 patients with OSAHS, 65 cases of OSAHS with T2DM patients, 20 patients with T2DM, and 32 cases of healthy control group were observed in this study. The serum levels of TNF-α and ET were detected by double antibody sandwich ELISA, the content of TNF-α and ET were compared between OSAHS group and OSAHS + T2DM group. It were also compared before and after treatment of CPAP or surgery. RESULT: TNF-α level is higher in OSAHS+T2DM group than that in the OSAHS group, T2DM group and the control group (P < 0.05); TNF-α level in OSAHS group and the T2DM group are higher than that in the control group (P < 0.05), but there was no difference in TNF-α level between the OSAHS group and the T2DM group. There was also no difference in ET level of the four groups. There were significant differences of TNF-α before and after treatment of CPAP or surgery in OSAHS group and OSAHS+T2DM group (P < 0.05). But there was no significant differences of ET before and after treatment of CPAP or surgery in the OSAHS+T2DM group (P > 0.05). CONCLUSION TNF-α may be involved in the development of OSAHS and T2DM, while ET may have little effect on the occurrence and development of OSAHS and T2DM.
Antibodies ; Diabetes Mellitus, Type 2 ; blood ; complications ; Endothelins ; blood ; Enzyme-Linked Immunosorbent Assay ; Humans ; Sleep Apnea, Obstructive ; blood ; complications ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the clinical significance of dynamic changes in the serum inflammatory cell factors consisting of β-endorphin (β-EP) , endothelins (ET) , tumor necrosis factor (TNF) , and nitric oxide (NO) after acute paraquat poisoning (APP).

METHODSThe 26 patients with APP (as observation group) were treated and the serum levels of plasma β-EP, ET, TNF, and NO were measured simultaneously. The 20 healthy volunteers from relatives of the patients (as control group) were also included in the study and their serum levels of β-EP, ET, TNF, and NO were measured.

RESULTSIn the 26 patients with APP, 10 were cured and 16 died. The serum levels of β-EP, ET, NO, and TNF in the 10 cured patients increased significantly immediately after admission, reached the peak values on day 2, and then decreased gradually and returned to the normal ranges after day 9. The serum levels of β-EP, ET, NO, and TNF in the 16 dead patients increased significantly on admission and kept rising in the course of treatment. The dead patients had significantly increased serum levels of β-EP, ET, NO, and TNF compared with the cured patients (all P<0.01).

CONCLUSIONCompared with those in cured patients with APP, the serum levels of β-EP, ET, NO, and TNF in dead patients with APP are significantly higher, keep rising, and maintain at high levels, indicating a severe condition.

Case-Control Studies ; Endothelins ; blood ; Humans ; Nitric Oxide ; blood ; Paraquat ; poisoning ; Tumor Necrosis Factor-alpha ; blood ; beta-Endorphin ; blood

OBJECTIVETo investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension.

METHODSA randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment.

RESULTSAfter treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05).

CONCLUSIONIn patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.

Aged ; Atorvastatin Calcium ; C-Reactive Protein ; metabolism ; Double-Blind Method ; Endothelins ; blood ; Exercise Tolerance ; drug effects ; Female ; Heart Failure ; complications ; drug therapy ; physiopathology ; Heptanoic Acids ; pharmacology ; Humans ; Hypertension ; complications ; drug therapy ; physiopathology ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Prospective Studies ; Pyrroles ; pharmacology

OBJECTIVETo study the changes of cardiovascular regulating factors in rats during recovery of aerobic exhaustive exercise.

METHODSSixty male Wistar rats were randomly divided into control group, 1 h-exercise group, 3 h-exercise group, exhausted group, 2 h-recovery group and 12 h-recovery group. The rats were killed at corresponding times for each group after an 8-week-long treadmill training, and the levels of NO, ET, ANP and TXB2 in plasma were measured in each group.

RESULTSNO/ET ratio of 1 h-exercise group was significantly higher than that in control group (P < 0.01), while it was significantly decreased in 3 h-exercise group and exhausted group (P < 0.05). ANP contents in rat plasma were significantly higher in 3 h-exercise group, exhausted group and 2 h-recovery group than that in control group (P < 0.05 or P < 0.01). The concentration of TXB2 in plasma was significantly increased in 3 h-exercise group, exhausted group and 2 h-recovery group (P < 0.05).

CONCLUSIONChanges in cardiovascular regulating factors after exhaustive exercise may lead to deficiency of coronary circulation blood/oxygen supply, which may cause exercise-induced fatigue.

Animals ; Atrial Natriuretic Factor ; blood ; Cardiovascular System ; physiopathology ; Endothelins ; blood ; Exercise Test ; Fatigue ; blood ; Male ; Nitric Oxide ; blood ; Physical Conditioning, Animal ; Rats ; Rats, Wistar ; Thromboxane B2 ; blood

BACKGROUND AND OBJECTIVES: There are several evidences of reduced cochlea blood flow after noise exposure in the cochlea. However, the pathophysiology of blood flow change is still obscure, and endothelins, proteins that constrict blood vessels and play a key role in vascular homeostasis using its receptors may have importance in this respect. In this study, we investigated the expression changes of endothelin-1 (ET-1), endothelin receptor A (ETAR) and B (ETBR) according to auditory threshold change after noise exposure. MATERIALS AND METHOD: Mice were exposed to different noise to generate transient (group 2) and permanent threshold shift (group 3), respectively. Auditory threshold shifts were evaluated with auditory brainstem response and expression changes of ET-1, ETAR and ETBR after noise exposure were evaluated by immunohistochemistry and real time RT-PCR. RESULTS: After noise exposure, the increased ET-1, ETAR and ETBR immunoreactivities were observe in stria vascularis, spiral ligament and spiral ganglion neuron. ET-1 mRNA expressions increased after noise exposure in both group 2 and group 3 compared to those of the control group. At 2 weeks after noise exposure, however, the ET-1 mRNA expressions in group 3 increased compared to that of the control but decreased compared to that of group 2. On the other hand, ETAR mRNA expression increased at 2 weeks after noise exposure in both groups, just after noise exposure in group 2 and at 2 weeks after noise exposure in group 3. CONCLUSION: These results suggest that expression changes of ET-1, ETAR and ETBR might be associated with hearing threshold shift and recovery after noise exposure in the cochlea.
Animals ; Auditory Threshold ; Blood Vessels ; Cochlea ; Endothelin-1 ; Endothelins ; Evoked Potentials, Auditory, Brain Stem ; Hand ; Hearing ; Homeostasis ; Immunohistochemistry ; Mice ; Neurons ; Noise ; Proteins ; Receptors, Endothelin ; RNA, Messenger ; Spiral Ganglion ; Spiral Ligament of Cochlea ; Stria Vascularis

BACKGROUND: Interfering RNA (iRNA) represents a recent breakthrough in effective blocking of the target genes in mammalian cells. Angiotensin-converting enzyme (ACE) has been shown to play an important role in the pathogenesis of hypertension. The purposes of this study were to investigate the effects on blood pressure, myocardial hypertrophy and gene expressions of iRNA targeting ACE. METHODS: Twelve week old male Wistar-Kyoto rats were grouped as follows: control group (C group), spontaneously hypertensive rat (SHR) group (H group), and ACE-iRNA group (A group) in which SHR was treated with recombinant lentiviral vectors carrying small hairpin RNA targeting ACE. Reverse transcription-polymerase chain reaction and western blot analysis of ACE, endothelin (ET)-1, angiotensin (AT) II receptor type 1A, neutrophil cytosolic factor, caspase 3, Bax, and Bcl-2 were performed in the heart tissues. Serum AT, ACE, and high sensitive-C reactive protein were estimated. RESULTS: Systolic blood pressure was significantly decreased in the A group compared with the H group in weeks 3 and 5. Serum AT level was significantly lower on day 1, weeks 3 and 5 after ACE-iRNA treatment. ACE protein contents were significantly lower after ACE-iRNA treatment in week 5. ET-1 and Bcl-2 protein contents were significantly lower after ACE-iRNA treatment in weeks 3 and 5. Bax protein contents were significantly lower after ACE-iRNA treatment in week 3. CONCLUSIONS: Recombinant lentiviral vectors carrying shRNA targeting ACE prevented hypertension. Serum AT and gene expressions such as ACE, ET-1, Bax, and Bcl-2 were significantly decreased after ACE-iRNA treatment.
Angiotensins ; Animals ; bcl-2-Associated X Protein ; Blood Pressure ; Blotting, Western ; Caspase 3 ; Cytosol ; Endothelins ; Gene Expression ; Heart ; Humans ; Hypertension ; Hypertrophy ; Lentivirus ; Lifting ; Male ; Neutrophils ; Rats ; Rats, Inbred SHR ; RNA ; RNA Interference ; RNA, Small Interfering

OBJECTIVETo observe the effects of Di' ao Xinxuekang Soft Capsule (DK) on the plasma levels of superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin (ET) in patients with coronary heart disease (CHD), and to study its underlying mechanisms.

METHODSTotally 100 patients with CHD confirmed by coronary angiography were randomly assigned to two groups, the control group (60 cases) and the DK treatment group (40 cases). Patients in the control group received conventional therapy, while those in the DK treatment group received DK additionally. The therapeutic course for all was 3 months. The plasma levels of SOD, MDA, ET, and NO were determined pre-treatment, 4, 8, and 12 weeks after treatment.

RESULTSCompared with before treatment, the serum levels of SOD and NO increased and the levels of MDA and ET decreased at each time point. Besides, better effects were obtained in the DK treatment group (P < 0.05).

CONCLUSIONDK possibly played a role in inhibiting lipid peroxidation and improving the endothelial dysfunction.

Aged ; Coronary Disease ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Endothelins ; blood ; Endothelium, Vascular ; physiopathology ; Female ; Humans ; Lipid Peroxidation ; Male ; Malondialdehyde ; blood ; Middle Aged ; Nitric Oxide ; blood ; Phytotherapy ; Superoxide Dismutase ; blood

OBJECTIVETo study the changes of pulmonary vascular remodeling in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) in neonatal rats.

METHODSNinety-six newborn Wistar rats were randomly divided into an HPH group (hypoxia exposure) and a control group (room air exposure). The mean pulmonary arteria pressure (mPAP), right ventricle hypertrophy index (RVHI), and vascular remodeling indexes MT% and MA% were measured 3, 5, 7, 10, 14 and 21 days after exposure (n=8 each time point). The ultrastructure of pulmonary vascular was observed under a transmission electron microscope.

RESULTSmPAP in the HPH group 3, 5, 7, 10, 14 and 21 days after hypoxia exposure increased compared with the control group (P<0.05). With the prolonged hypoxia time, mPAP in the HPH group increased more significantly. MT%, MA% and RVHI increased significantly in the HPH group after 7 days of hypoxia exposure in a time-dependent manner compared with the control group (P<0.05). The transmission electron microscopy demonstrated that small pulmonary arterials became thickened, endothelial cell hyperplasia and degeneration, and organelles increased in the HPH group after 7 days of hypoxia exposure. Besides, collagen deposition in the extracellular matrix and the changes of pulmonary vascular remodeling were observed.

CONCLUSIONSmPAP increases between 3 and 5 days of hypoxia exposure, resulting from pulmonary vascular spasm caused by hypoxia. After hypoxia of 7 days, the mPAP increases more significantly, pulmonary vascular remodeling occurs, and right ventricle becomes irreversibly hypertrophic. These changes may be intensified as the prolonged hypoxia time.

Animals ; Animals, Newborn ; Blood Pressure ; Endothelins ; physiology ; Hypertension, Pulmonary ; etiology ; Hypertrophy, Right Ventricular ; etiology ; Hypoxia ; complications ; Pulmonary Artery ; pathology ; ultrastructure ; Rats ; Rats, Wistar

OBJECTIVETo observe the effects of training on plasma content of NO, ET and NO/ET system in rats fed with high methionine diets.

METHODSMale Wistar rats were randomly divided into normal diet group (CR), high methionine diet group (MR) and high methionine diet plus 90 min swimming group (T+ MR). Rats in MR and T+ MR group were fed with the diet which contained 3%of methionine for eight weeks, but rats in control group were fed with ordinary diet. After breeding for eight weeks homocysteine (Hcy) level, T-NOS, NO and ET were measured.

RESULTSPlasma homocysteine of MR increased twofold as compared with that of CR,whereas plasma NO/ET of MR descended significantly (P < 0.05), suggesting that hyperhomocysteinemia was induced by the high methionine diet, and plasma NO/ET system was out of balance. Plasma homocysteine content of T+ MR obviously descended, plasma T-NOS, NO and NO/ET ascended obviously (P < 0.05) as compared with that of MR, and the above indicators of group T + MR were not different as compared with that of CR (P > 0.05).

CONCLUSIONProper training can descend plasma homocysteine level of rats fed with high methionine diet and better balance between NO and ET to prevent developing of hyperhomocysteinemia.

Animals ; Dietary Supplements ; Endothelins ; blood ; Hyperhomocysteinemia ; prevention & control ; Male ; Methionine ; administration & dosage ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Wistar ; Swimming ; physiology