1.The involvement of K+ channels and the possible pathway of EDHF in the rabbit femoral artery.
Seong Chun KWON ; Wook Bum PYUN ; Gi Young PARK ; Hee Kyung CHOI ; Kwang Se PAIK ; Bok Soon KANG
Yonsei Medical Journal 1999;40(4):331-338
Experiments were designed to characterize the cellular mechanisms of action of endothelium-derived vasodilator substances in the rabbit femoral artery. Acetylcholine (ACh, 10(-8)-10(-5) M) induced a concentration-dependent relaxation of isolated endothelium-intact arterial rings precontracted with norepinephrine (NE, 10(-6) M). The ACh-induced response was abolished by the removal of endothelium. NG-nitro-L-arginine (L-NAME, 10(-4) M), an inhibitor of NO synthase, partially inhibited ACh-induced endothelium-dependent relaxation, whereas indomethacin (10(-5) M) showed no effect on ACh-induced relaxation. 25 mM KCl partially inhibited ACh-induced relaxation by shifting the concentration-response curve and abolished the response when combined with L-NAME and NE. In the presence of L-NAME, ACh-induced relaxation was unaffected by glibenclamide (10(-5) M) but significantly reduced by apamin (10(-6) M), and almost completely blocked by tetraethylammonium (TEA, 10(-3) M), iberiotoxin (10(-7) M) and 4-aminopyridine (4-AP, 5 x 10(-3) M). The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10(-5) M) and miconazole (10(-5) M) also significantly inhibited ACh-induced relaxation. Ouabain (10(-6) M), an inhibitor of Na+, K(+)-ATPase, or K(+)-free solution, also significantly inhibited ACh-induced relaxation. ACh-induced relaxation was not significantly inhibited by 18-alpha-glycyrrhetinic acid (18 alpha-GA, 10(-4) M). These results of this study indicate that ACh-induced endothelium-dependent relaxation of the rabbit femoral artery occurs via a mechanism that involves activation of Na+, K(+)-ATPase and/or activation of both the voltage-gated K+ channel (Kv) and the large-conductance, Ca(2+)-activated K+ channel (BKCa). The results further suggest that EDHF released by ACh may be a cytochrome P450 product.
Acetylcholine/pharmacology
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Animal
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Biological Factors/physiology*
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Female
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Femoral Artery/physiology*
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Femoral Artery/drug effects
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In Vitro
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Male
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Potassium Channels/physiology*
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Rabbits
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Vasodilation/physiology
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Vasodilator Agents/pharmacology
2.Principal component analysis and integral methods of cerebral vascular hemodynamic parameters.
Yi-feng CAO ; Gui-qing WANG ; Jiu-yi HUANG ; Xiu-e GUO ; Zuo GUO ; Yong-ju YANG ; Chun-hong FENG
Chinese Journal of Epidemiology 2003;24(9):798-800
OBJECTIVETo establish a predicting model for stroke according to cerebral vascular hemodynamic indexes and major risk factors of stroke.
METHODSParticipants selected from a stroke cohort with 25,355 population in China. The first step was to carry out principal component analysis using CVHI. Logistic regression with principal component and main risk factors of stroke were then served as independent variables and stroke come on as dependent variables. The predictive model was established according to coefficient of regression and probability of each participant was also estimated. Finally, ROC curve was protracted and predictive efficacy was measured.
RESULTSThe accumulative contribution rates of four principal components were 58.1%, 79.4%, 88.4% and 94.6% respectively. Seven variables were being selected into the equation with the first to fourth principal component as history of hypertension, age and sex. Area under ROC curve was 0.855 and optimal cut-off point was probability over 0.05. Sensitivity, specificity and accuracy of stroke prediction were 80.7%, 78.5% and 78.5% respectively.
CONCLUSIONThe model established by principal component and regression could effectively predict the incidence of stroke coming on.
Brain ; blood supply ; Hemodynamics ; physiology ; Humans ; Logistic Models ; Models, Biological ; Principal Component Analysis ; Risk Factors ; Stroke ; etiology
3.Modeling of p53 signaling pathway based on S-system equations.
Shunhui LIU ; Changli TAO ; Zhenyi HUANG ; Shulin HUANG
Journal of Biomedical Engineering 2010;27(3):505-510
p53, as a transcription factor, is an important tumor suppressor gene and plays the key role in the p53-dependent gene regulatory network. Therefore, it is important to understand its biological function at the level of the whole system. In this paper, based on KEGG database and related literatures in English and Chinese, the interaction mode and quantitative relationship of the related molecules involved in p53 signaling pathway were extracted. By using S-system equations and 'Simulink' toolbox of Matlab7.0, a dynamic model of p53 signaling pathway was developed, and the dynamic regulatory characteristics of p53 signaling pathway were analyzed on model simulation. The results were in accord with the literatures and could reflect quantitatively the complex regulatory relationship between the interacting molecules involved in p53 signaling pathway. In addition, model simulation helped us find and identify the key molecules in this signaling pathway. Thus, this model can be used as a basis for the follow-up study of the relationship by precise and quantitative assessment.
Algorithms
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Computer Simulation
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Gene Expression Regulation
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Humans
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Models, Biological
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Signal Transduction
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physiology
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Transcription Factors
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genetics
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metabolism
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Tumor Suppressor Protein p53
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genetics
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physiology
4.Differences in nitric oxide release and endothelium-derived hyperpolarizing factor-mediated hyperpolarization between human radial artery and saphenous vein.
Zhi-gang LIU ; Xiao-cheng LIU ; Guo-wei HE
Chinese Journal of Surgery 2011;49(12):1128-1131
OBJECTIVETo compare the differences in nitric oxide (NO) release and endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization between human radial artery (RA) and saphenous vein (SV) through direct measurement of NO and membrane potential.
METHODSRA (n = 8), SV (n = 23), and surgical prepared SV (PV, n = 9, dilatation with normal saline solution at a pressure of 100 - 600 mmHg, 1 mmHg = 0.133 kPa) segments (5 mm long) taken from patients undergoing coronary artery bypass grafting were placed in an organ chamber. The NO-sensitive electrode and intracellular glass microelectrode was used to directly measure the NO release and the membrane potential changes in response to acetylcholine (ACh) and bradykinin (BK) before and after incubation with NG-nitro-L-arginine, indomethacin, and oxyhemoglobin.
RESULTSThe basal release of NO in RA [(11.9 ± 1.8) nmol/L] was significantly greater than that in SV [(9.9 ± 2.8) nmol/L, P = 0.041]. BK-induced NO release in RA was lower than that in SV [for BK 10(-7) mol/L: (25.8 ± 3.6) nmol/L vs. (43.7 ± 8.2) nmol/L, P = 0.006]. Both basal and ACh- or BK-induced NO release in PV were significantly reduced [basal release: PV (3.4 ± 1.4) nmol/L; P = 0.006 vs. RA; P = 0.002 vs. SV; stimulated release: for ACh 10(-5) mol/L: PV (4.8 ± 3.2) nmol/L; vs. RA (28.6 ± 7.9) nmol/L, P = 0.005; vs. SV (27.4 ± 3.7) nmol/L, P = 0.003; for BK 10(-7) mol/L: PV (7.0 ± 3.6) nmol/L; vs. RA (25.8 ± 3.6) nmol/L, P = 0.016; vs. SV (43.7 ± 8.2) nmol/L, P = 0.004]. EDHF-mediated hyperpolarization was greater in RA than that in SV [ACh 10(-5) mol/L: (-9.7 ± 1.9) mV vs. (-4.5 ± 1.1) mV, n = 17, P = 0.002].
CONCLUSIONSRA is superior to SV in terms of NO basal release and EDHF-mediated endothelial function. Surgical preparation and pressure dilatation may severely impair the NO-mediated endothelial function of SV, which may contribute to the poor long-term patency of SV coronary graft.
Biological Factors ; metabolism ; Endothelial Cells ; metabolism ; physiology ; Endothelium, Vascular ; cytology ; metabolism ; Female ; Humans ; Male ; Membrane Potentials ; physiology ; Middle Aged ; Nitric Oxide ; metabolism ; Radial Artery ; cytology ; Saphenous Vein ; cytology
5.Detection of bronchial function of NHBD lung following one-h warm ischemia by organ bath model.
Yang, YANG ; Song, ZHAO ; Qiuming, LIAO ; Jianjun, WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(3):340-3
This study investigated the feasibility and effects of organ bath to be used for detection of bronchial function of non-heart-beating donor (NHBD) lung after 1-h warm ischemia. Sixteen Swedish pigs were divided into two groups randomly: heart-beating donor (HBD) group and NHBD with 1-h warm ischemia (NHBD-1 h) group. The bronchial rings whose lengths and inner diameters were both 1.5 mm were obtained from isolated left lungs of all the pigs. Acetylcholine, arachidonic acid natrium and papaverine were used to test and compare the contractile and relaxant function of bronchial smooth muscles and epithelium-dependent relaxation (EpiDR) response between HBD and NHBD-1 h groups. The results showed that there was no significant difference in the values of bronchial precontraction between HBD and NHBD-1 h groups (5.18+/-0.07 vs 5.10+/-0.11 mN, P>0.05). No significant difference in the values of EpiDR responses between HBD and NHBD-1 h groups (1.26+/-0.05 vs 1.23+/-0.07 mN, P>0.05) was observed either. During the process of EpiDR induction, the rings had no spontaneous relaxation in two groups. In addition, papaverine solution completely relaxed the bronchial smooth muscles of all bronchial rings. It was concluded that after warm ischemia for 1 h, the contractile and relaxant abilities of bronchial smooth muscles, and the epithelium-dependent adjustment both kept intact. Organ bath model could be a liable and scientific way to evaluate the bronchial function of NHBD lung.
Biological Factors/metabolism
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Bronchi/metabolism
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Bronchi/*physiology
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Heart Arrest/*metabolism
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Heart Arrest/physiopathology
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Lung Transplantation
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Models, Biological
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Muscle Relaxation/physiology
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Organ Preservation/*methods
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Random Allocation
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Reperfusion Injury/prevention & control
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Swine
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Tissue and Organ Procurement
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Warm Ischemia/*methods
6.Bone adaptive digital analysis for femur bone being in disuse and overload condition.
Journal of Biomedical Engineering 2008;25(5):1074-1078
Mature femur bone, through the process of bone remodeling, renews itself and adapts to mechanical load. In this study, a biomechanical model involving strain and other variable parameters was developed for bone remodeling and used to simulate the removal of bone mass and bone regeneration in the disuse and overload condition. The results exhibit that elastic modulus in bone lateral portion is decreasing and porosity is increasing for acquiring equilibrium strain. The conclusion of simulation for reality femur model is more accurate than what is obtained from simplified model or from only one volume element. These indicate the significance of acquiring scientific data to the development of consummate simulation model.
Adaptation, Physiological
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physiology
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Bone Remodeling
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physiology
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Computer Simulation
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Elasticity
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Femur
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diagnostic imaging
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physiology
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Finite Element Analysis
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Humans
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Models, Biological
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Porosity
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Stress, Mechanical
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Time Factors
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Tomography, X-Ray Computed
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Weight-Bearing
7.Study on effect of artificial CsB and its components on bile acid metabolism in rats with liver fibrosis and its mechanism.
Xing ZHANG ; Feng-Hua LI ; Ping LIU ; Jia LIU ; Shuang WANG
China Journal of Chinese Materia Medica 2013;38(22):3943-3948
Bile acid is a type of metabolite degraded from cholesterol in liver. Its accumulation in liver could cause liver diseases, liver damage and liver fibrosis. In this experiment, dimethyl nitrosamine (DMN) liver fibrosis was established in rats. The rats were delivered into the normal group, the model group and four treated groups. After the four-week modeling, the treated groups were orally administered with drugs for 2 weeks, whereas the model and normal groups were given equal amount of sterile water at the same time. In the experiment, serum bile acid was taken the as marker, and liver function indexes and changes in bile acid metabolism were detected and observed to identify liver damage-related bile acid targets. It was the first time to evaluate the reverse effect of artificial CsB and its components on liver fibrosis in rats with bile acid metabolic level, and discuss its potential mechanism. The main study contents and results are as follows: a quantitative analysis was made on totally 17 endogenous bile acids, including taurocholic acid conjugated bile acid, glycine conjugated bile acid and free bile acid, and a liver damage evaluation was made for the model according to the detection of serum biochemical indexes and the pathological biopsy. After modeling, ALT, AST activity and TBil content significantly increased, whereas Alb significantly decreased. According to the pathological biopsy HE staining, the model group showed damage in normal hepatic lobule structure, liver cell edema and connective tissue proliferation in portal area; The treated groups showed mitigation in pathological changes to varying degrees. Cordyceps sinensis and its components may impact the bile acid metabolism in rats by activating HDCA, TCA, TCDCA, TLCA, TUDCA, UDCA, THDCA metabolim-related receptors or blocking relevant signaling pathway.
Animals
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Bile Acids and Salts
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metabolism
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Biological Factors
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administration & dosage
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Cordyceps
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chemistry
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physiology
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Humans
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Liver Cirrhosis
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drug therapy
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metabolism
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Male
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Moths
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chemistry
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microbiology
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Rats
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Rats, Wistar
8.Role of phospholipase D1 in glucose-induced insulin secretion in pancreatic beta cells.
Wei na MA ; Shin Young PARK ; Joong Soo HAN
Experimental & Molecular Medicine 2010;42(6):456-464
As glucose is known to induce insulin secretion in pancreatic beta cells, this study investigated the role of a phospholipase D (PLD)-related signaling pathway in insulin secretion caused by high glucose in the pancreatic beta-cell line MIN6N8. It was found that the PLD activity and PLD1 expression were both increased by high glucose (33.3 mM) treatment. The dominant negative PLD1 inhibited glucose-induced Beta2 expression, and glucose-induced insulin secretion was blocked by treatment with 1-butanol or PLD1-siRNA. These results suggest that high glucose increased insulin secretion through a PLD1-related pathway. High glucose induced the binding of Arf6 to PLD1. Pretreatment with brefeldin A (BFA), an Arf inhibitor, decreased the PLD activity as well as the insulin secretion. Furthermore, BFA blocked the glucose-induced mTOR and p70S6K activation, while mTOR inhibition with rapamycin attenuated the glucose induced Beta2 expression and insulin secretion. Thus, when taken together, PLD1 would appear to be an important regulator of glucose-induced insulin secretion through an Arf6/PLD1/mTOR/p70S6K/Beta2 pathway in MIN6N8 cells.
ADP-Ribosylation Factors/metabolism/physiology
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Animals
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Basic Helix-Loop-Helix Transcription Factors/metabolism/physiology
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Cells, Cultured
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Gene Expression Regulation, Enzymologic/drug effects
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Glucose/*pharmacology
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Insulin/*secretion
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Insulin-Secreting Cells/*drug effects/enzymology/metabolism/secretion
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Intracellular Signaling Peptides and Proteins/metabolism/physiology
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Mice
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Models, Biological
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Oligodeoxyribonucleotides, Antisense/pharmacology
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Phospholipase D/antagonists & inhibitors/genetics/metabolism/*physiology
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Protein-Serine-Threonine Kinases/metabolism/physiology
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Ribosomal Protein S6 Kinases, 70-kDa/metabolism/physiology
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Signal Transduction/drug effects/genetics
9.Minimally modified LDL induced impairment of endothelium-dependent relaxation in mesenteric arteries of mice.
Gen CHEN ; Xu-ping QIN ; Jie LIN ; Jun-jie WANG ; Nan ZHOU ; Jie LI
Acta Pharmaceutica Sinica 2013;48(11):1657-1664
This study is to investigate the impairment and possible mechanism of endothelium-dependent relaxation of mice mesenteric arteries induced by mmLDL. Wire myography was employed to examine endothelial function of mesenteric arteries. Ultramicrostructure of mesenteric vascular beds were detected by transmission electron microscope. The results showed that endothelium cell edema and peeling, vascular elastic membrane fracture traces in mmLDL group. Endothelium-dependent relaxation was decreased in a time-dependent and dose-dependent manner by using mmLDL, compared with normal arteries. In endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation, the Rmax and pIC50 were decreased from (63 +/- 5) % and 6.42 +/- 0.09 of normal saline control to (31 +/- 3) % and 5.67 +/- 0.07 in mmLDL group (P < 0.001, P < 0.001), respectively. In nitric oxide (NO)-mediated relaxation, the Rmax and pIC50 were decreased from (45 +/- 4) % and 5.93 +/- 0.08 in normal saline control to (32 +/- 4) % and 5.43 +/- 0.11 in mmLDL group (P < 0.05, P < 0.01), respectively. There is no significant alteration of prostacyclin I2 (PGI2) pathway between these two groups. In conclusion, mmLDL induced the impairment of the ultramicrostructure of mesenteric vascular endothelium cell as well as the endothelium-dependent relaxation. The latter includes the dysfunction of NO- and EDHF pathway mediated endothelium-dependent relaxation.
Animals
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Biological Factors
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antagonists & inhibitors
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physiology
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Dose-Response Relationship, Drug
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Endothelial Cells
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drug effects
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ultrastructure
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Epoprostenol
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antagonists & inhibitors
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physiology
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Female
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Lipoproteins, LDL
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administration & dosage
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pharmacology
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Male
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Mesenteric Arteries
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cytology
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physiology
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ultrastructure
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Mice
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Mice, Inbred ICR
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Microscopy, Electron, Transmission
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Nitric Oxide
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antagonists & inhibitors
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physiology
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Vasodilation
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drug effects
10.Role of endothelium-derived hyperpolarizing factor in shear stress-induced endothelium-dependent relaxations of rats.
Hui-Ying ZHAO ; Quan LIU ; Bao-Rong CHI
Acta Pharmaceutica Sinica 2005;40(6):491-495
AIMTo investigate the role and mechanism of endothelium-derived hyperpolarizing factor (EDHF) in shear stress induced vasorelaxation of rat mesenteric artery.
METHODSThe changes in vessel diameter in response to variable flow (0-300 microL.min(-1)) were continuously examined. The contribution of prostacyclin (PGI2), NO and EDHF to shear stress induced relaxation were analyzed by inhibitory effects of indomethacin, N(G)-nitro-L-arginine (L-NA) and KCl. The nature and hyperpolarizing mechanism of EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K+ channels.
RESULTSThe shear stress-induced relaxation were endothelium dependent and the contribution of NO was more prominent in large mesenteric arteries (400-500 microm) than that in resistance arteries (150-250 microm), whereas that of EDHF was noted in both-sized blood vessels. Tetrabutylammonium (a nonselective inhibitor of K channels) almost abolished, whereas the combination of charybdotoxin (an inhibitor of both large and intermediate-conductance Ca2+-activated K channels) and apamin (an inhibitor of small-conductance Ca2+-activated K channels) significantly inhibited the EDHF-mediated component of the shear stress-induced relaxations.
CONCLUSIONEDHF plays an important role in shear stress-induced endothelium-dependent relaxations, and K channels especially calcium-activated K channels appear to be involved.
Animals ; Apamin ; pharmacology ; Biological Factors ; physiology ; Charybdotoxin ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; Endothelium, Vascular ; drug effects ; physiology ; In Vitro Techniques ; Large-Conductance Calcium-Activated Potassium Channels ; antagonists & inhibitors ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Nitric Oxide ; physiology ; Potassium Channel Blockers ; pharmacology ; Proadifen ; pharmacology ; Quaternary Ammonium Compounds ; pharmacology ; Rats ; Rats, Wistar ; Small-Conductance Calcium-Activated Potassium Channels ; antagonists & inhibitors ; Vasodilation ; drug effects