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@#Objective To investigate the effect of microparticles(MPs)derived from bone marrow mesenchymal stem cells(BMSCs) on myocardial hypertrophy and its mechanism.Methods The osteogenic differentiation and adipogenic differentiation of mesenchymal stem cells(MSCs) were induced. After isolation and purification,the morphological characteristics were observed by transmission electron microscope,and the MPs surface antigen was identified by flow cytometry. Myocardial hypertrophy model was induced by using isoprenaline(ISO)in rats,which were measured for the cardiac structure and function by echocardiography,and then detected for various indexes of the heart and isolated left ventricle. Single ventricular myocytes of rats were acutely isolated and divided into control group(Control group),cardiomyocyte hypertrophy group(ISO group),MPs group(MPs group),and MPs supernatant group(Supernatant group). The mRNA expressions of atrial natriuretic peptide(ANP)and B-type natriuretic peptide(BNP)were detected by qRTPCR. The expression levels of calmodulin-dependent protein kinaseⅡ（CaMKⅡ）and phosphorylated calmodulin-dependent protein kinaseⅡ（p-CaMKⅡ）were detected by ELISA. The L-type calcium current(LCa-L)in single ventricular myocyte of various groups was recorded by whole-cell patch clamp.Results The bone nodules of MSCs osteogenic differentiation turned red after alizarin red staining,and lipid droplets of adipogenic differentiation turned red after oil red O staining;Under transmission electron microscope,MPs membrane had a complete structure,a clear outline and a diameter of about200 nm;The positive rates of CD29 and CD90 on the surface of MPs were(98. 24 ± 0. 82)% and(97. 69 ± 1. 83)%,respectively. Compared with Control group,the left ventricular end diastolic dimension(LVEDD)reduced signifi-cantly(t =5. 065,P < 0. 05),while the interventricular septum end-diastolic dimension(IVSd),left ventricular posterior wall dimension(LVPWd),heart weight to body weight ratio(HW/BW),and heart weight to tibial length ratio(HW/Tibia)significantly increased in ISO group(t = 4. 013,2. 368,4. 392,5. 043 and 6. 120,respectively,each P < 0. 05),indicating that the hypertrophic model was successfully established. The expression levels of ANP and BNP mRNA in hypertrophic cardiomyocytes of rats in ISO group were significantly higher than those in Control group(t = 25. 120 and18. 261,respectively,each P < 0. 01);While the expression levels of ANP and BNP mRNA in MPs group significantly reduced after incubation with 48 μg/mL MPs for 48 h compared with ISO group(t = 12. 110 and 3. 526,respectively,each P < 0. 05);The expression levels of CaMK Ⅱand p-CaMKⅡ in ISO group were significantly higher than those in Control group(t = 3. 278 and 4. 181,respectively,each P < 0. 05),while the expression of p-CaMK Ⅱ in MPs group decreased significantly(t = 5. 420,P < 0. 05);The calcium current density in ISO group was significantly higher than that in Control group(t = 15. 261,P < 0. 01),while that in MPs group was significantly lower than that in ISO group(t =6. 216,P < 0. 05).Conclusion MSC-MPs can significantly inhibit ISO-induced cardiomyocyte hypertrophy in rats,which is related to its down-regulation of cardiomyocyte CaMKⅡ and inhibition of L-type calcium channel.
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Aim To investigate the mechanism of RhoA/ROCK signaling pathway in abnormal aortic contractility in type 2 diabetes (T2DM) mice. Methods The experiment was divided into two groups, the control group (db/m mice) and the model group (db/db mice). Changes of the response to different methods were measured in aorta rings using a Multi Myograph System. At the same time, the protein expression changes of aortic smooth muscle contraction signaling pathway in mice were determined by Western method. Results Compared with the control group, the blood glucose and body weight levels of the mice in the T2DM group significantly increased, and the cardiac function was abnormal (P <0. 01). The contractile response of the aorta of the diabetic mice induced by the contractile agents Phe, 5-HT and CaCl
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【Objective】 To explore the effect of bisoprolol on ICa，Lin volume overload combined with pressure overload heart failure in rabbits. 【Methods】 Totally 82 male New Zealand rabbits （2.5-3.0 kg） were randomly divided into three groups： SO （sham group）， HF （heart failure group）， and BF （heart failure with bisoprolol treatment group）. HF rabbits were duplicated by aortic valve insufficiency procedure combined with abdominal aorta constriction procedure. Real-time PCR and Western blot analysis were performed to detect the expression of ICa，L in left ventricular myocytes. Left ventricular myocytes were isolated； then the cell membrane capacitance， the current density， activation and inactivation of ICa，L were recorded by whole cell patch clamp. 【Results】 ① Bisoprolol could improve the heart function of heart failure rabbits according to the measurement of echocardiography and BNP. ② The expressions of ICa，L mRNA and protein decreased significantly in heart failing rabbits （P<0.01）， but remained unaltered after chronic bisoprolol treatment （P>0.05）. ③ Membrane capacitance was larger in heart failing groups than in sham group （P<0.01）. ICa，L current density decreased greatly in HF group （P<0.01）. Bisoprolol treatment could not change Cm or ICa，L density （P>0.05）. V1/2 of activation curve negative shift enlarged window currents in heart failure groups. Bisoprolol treatment caused window currents to decrease. 【Conclusion】 Bisoprolol could reverse the heart function of heart failure rabbits and also affect the function of ICa，L.
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Objective:To investigate the effects of daurinsoline (DS) on L-type calcium channel Cav1.2 expressed in HEK293 cells.Methods:Cav1.2 was transferred into HEK293 cells using Lipofectamine 2000, and the effects of DS on Cav1.2 currents (ICav1.2) were analyzed by whole-cell patch clamp techniques. Results:DS at 1,3 and 10 μmol·L-1could inhibit the ICav1.2in HEK293 cells in a dose-dependent manner. The inhibitory rate was(14.68 ± 4.02) %,(32.37 ± 6.63) % and(59.63 ± 5.23) %,respectively. The inhibitory rate of DS at 3 μmol·L-1was 40 % of that of 3 μmol·L-1isradipine(a L-type calcium channel blocker). Conclusion:DS can inhibit the ICav1.2in HEK293 cells in a dose-dependent manner and the inhibition of DS is weaker than that of isradipine.
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Aim To investigate the effects of mono-clonal antibody NCX-2D2 on isoproterenol-induced ar-rhythmias in rat hearts, and to explore the electrophys-iological mechanism. Methods Using isoproterenol to establish in vitro and in vivo arrhythmic rat models to observe the effect of NCX-2D2 antibody on ventricular arrhythmias in rats. The whole-cell patch clamp tech-nique was used to investigate the effects of NCX-2D2 antibody on INa/Ca, ICa-Lat voltage-clamp mode and on DADs at current-clamp mode in single rat ventricular myocytes. Results 10 mg·L-1NCX-2D2 antibody significantly inhibited cardiac arrhythmias induced by ISO in vitro ( P<0.01) . 80 μg·kg-1NCX-2D2 anti-body markedly inhibit the occurrence of arrhythmias in ISO-induced anesthetized rats in vivo ( P <0.01 ) . 5 mg·L-1NCX-2D2 antibody partially inhibited the in-crease of INa/Ca(P<0.01) and the increase of ICa-L(P<0.01 ) , and could effectively inhibit ISO-induced DADs in rat ventricular myocytes ( P <0.05 ) . Con-clusions The sodium-calcium exchanger monoclonal antibody NCX-2D2 significantly inhibits isoproterenol-induced ventricular arrhythmias in rats. The mecha-nism against ventricular arrhythmias is mainly due to its inhibition of cardiomyocyte sodium-calcium exchanger and L-type calcium channel and marked suppression of DADs in rat ventricular myocytes.
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Aim To study whether there was arterial heterogeneity and association with L-type calcium channel (LCC) in different parts of arteries in re-sponse to certain vasoconstrictor. Methods The aor-ta, renal arteries and coronary arteries were dissected from rats. Arterial ring contractions induced by pheny-lephrine (Phe), 5-hydroxyl tryptamine (5-HT) or U46619 in concentration-dependent manner were meas-ured using the Multi Myograph system and the response to nifedipne was observed. Results (1) Phe had no obvious effect on the tension of coronary artery,but in-duced concentration-dependent vasoconstriction in aor-ta and renal artery,and pEC50of aorta was significantly higher than that of renal artery (P<0.05). The inhi-bition rate of nifedipine on the aortic contractile re-sponses was significantly higher than that of renal arter-y (P<0.05). (2) The contraction induced by 5-HT on aorta was not obvious, but was significant on renal artery and coronary artery. The inhibitory rate of nife-dipine on coronary artery vasoconstriction was signifi-cantly higher than that of renal artery (P <0.05). (3) U46619 could induce aorta,renal artery and coro-nary artery concentration- dependent contraction, but the Emaxof them were both higher than that of renal ar-tery (P<0.05). And the pEC50of aorta was the lar-gest (P<0.05). Nifedipine significantly inhibited the contraction of aorta, renal artery and coronary artery induced by U46619 with the greatest inhibitory rate on the coronary artery vasoconstriction and minimal inhibi-tion on aortic vasoconstriction. Conclusions The re-sponse to certain vasoconstrictor is different among aor-ta, renal artery and coronary artery in rats, and the contraction mediated by L-type calcium channel is also different.
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Aim To construct 3 D structure model of cardiac Cav1.2 channel and check its accuracy and re-liability.Methods Homology model of Cav1.2 chan-nel α1 subunit was constructed using SWISS-MODEL server.The model was submitted to an online testing server built by University of California and scored by it.The binding of Cav1.2 channel with blocker or drug was simulated by MOE software molecular docking pro-gram to check the model′s accuracy and reliability.Re-sults Both the target sequence Cav1.2 α1 C and the template sequence Cav1.1 α1 S searched by SWISS-MODEL server belonged to L-type Ca2+channel.Since the homology was 7 1.5% revealed by sequence align-ment,homology modeling was performed using automa-ted mode.L-type Ca2+ channel blockers Verapamil, Nifedipine and Diltiazem could bind to the 3 D structure model of Cav1.2 channel,while sodium channel bloc-ker TTX could not.Furthermore,active ingredient of traditional Chinese drug Praeruptorin A and Berberine could also bind to the 3D structure model of Cav1.2 channel.Conclusion The 3 D structure model of Cav1.2 channel was constructed successfully,which provides reliable materials for further studies and estab-lishes the foundation for the application of homology modeling in the study of 3 D structure prediction of ion channels.
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[ ABSTRACT] AIM:To investigate the mechanism of L-type calcium channel ( L-Ca2+)/calpain signal transduc-tion pathway in verapamil inversing resistance of papillary thyroid carcinoma to doxorubicin .METHODS:Human papillary thyroid carcinoma TPC-1 cells were cultured for 2 d.For determining the appropriate concentrations and treatment time of verapamil and doxorubicin , a compatibility test was conducted to detect the cell viability by CCK-8 assay.The cells were divided into control group , doxorubicin group , verapamil group and doxorubicin +verapamil group .The techniques of whole-cell patch-clamp was used to record L-Ca2+currents.The protein expression levels of calpain 1 and LC3 were detec-ted by Western blot .RESULTS: Compared with control group , the density of L-Ca2+current decreased in doxorubicin group and verapamil group (P<0.05).Compared with verapamil group , the density of L-Ca2+current decreased in doxo-rubicin+verapamil group (P<0.01).Compared with control group, the expression of calpain 1 decreased in doxorubicin group and verapamil group (P<0.05).Compared with doxorubicin group , the expression of calpain 1 decreased in doxo-rubicin+verapamil group (P<0.05).Compared with control group , the expression of LC3 increased in doxorubicin group and verapamil group (P<0.05).Compared with doxorubicin group , the expression of LC3 increased in doxorubicin +ver-apamil group ( P<0.01) .CONCLUSION:The drug resistance of TPC-1 cells to doxorubicin may be related to the in-crease in autophagic activity .Verapamil further increases autophagic activity of TPC-1 cells, resulting in autophagic death and inversing the resistance of TPC-1 cells to doxorubicin .The mechanism may be involved in L-Ca2+/calpain 1 signal transduction pathway of autophagy .
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Objective: To investigate the regulation of in vitro myocardial cell L type calcium channel of rats with active component of Shenfu Decoction and its combination. Methods: With Langendorff cardiac infusion, the single ventricular myocardial cell with acute enzymylosis approach was acquired and the voltage current of L type calcium channel was recorded with whole cell patch technique. Results: The active ginsenosides Re (3, 10, 30, and 100 μmol/L), and Rg1 (10 and 100 μmol/L) can reversibly reduce L type calcium current in a dose dependant manner, Rb1 (10 and 100 μmol/L) has no effect on L type calcium current; the active component aconine (10 and 100 μmol/L) of aconite could irreversibly enhance L type calcium current in a dose dependant manner; The combination of ginsenosides Re (20 μmol/L) and Rg1 (80 μmol/L) also reduced the L type calcium current, which is more significant than either ginsenosides Rg1 and Re; The inhibitory rate of the combination of ginsenosides Rg1, Re and aconine (100 μmol/L) has no difference from the combination of ginsenosides Rg1 and Re. Conclusion: The active component ginsenosides Rg1 and Re of Shenfu Decoction can reduce the L type calcium current, while aconine can irreversibly enhance the L type calcium current; The combination of ginsenosides Rg1 and Re can obviously increase the reduction of L type calcium current, while the combination of ginsenosides Rg1, Re and anonine can not change the reduction of L type calcium current.
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Objective In this research we established rapid atrial pacing rabbit models, to investigate the effects of simvastatin on changes of early atrial effective refractory period (AERP) and protein expression of atrial α1c sub-unit of L-type calcium channel on atrial remodeling. Methods 42 rabbits were randomly divided into 3 groups:control group,rapid pacing group and simvastatin group,simvastatin 5 mg/( kg·d) was given intragastrically daily for two weeks before electrophysiology study in simvastatin group, normal saline was given intragastrically in control and rapid pacing group instead. Control group with no pacing, in simvastatin group and rapid pacing group, right atrium was paced at 800 beats/min for 8 hours to establish acute atrial fibrillation models, right atrial effective re-fractory period(AERP)was measured at the basic cycle length of 200 ms and 150 ms before pacing and 1,2,4,6, and 8 hours after the onset of the pacing, the changes of rate adaptation of AERP (AERP200-AERP150) were ana-lyzed . Right atrium tissue was obtained for measurement of protein expression of atrialα1 c subunit of L-type calcium channel by Western blot. Simultaneously,lipid levels in each group was examined. Results No significant differ-ence in lipid levels among three groups was observed. The AERP was shortened and the rate adaptation of AERP (AERP200-AERP150) disappeared during pacing compared with those before pacing(P<0.05). The shortening of AERP was reversed and AERP200-AERP150 was maintained in simvastatin group. Compared with the control group,the protein expression levels of atrial α1c subunit of L-type calcium channel decreased significantly after 8 hours pacing in rapid pacing group(P<0.01). The protein expression levels of simvastatin group decreased insig-nificantly . Conclusion Atrial rapid pacing can induce the shortening of the AERP and the losing of adaptability to the frequency of AERP,pretreatment with simvastatin can improve the degree significantly and maintain the adapta-bility to frequence basically. The protein expression levels of atrial α1c subunit of L-type calcium channel de-creased significantly after 8 hours pacing,pretreatment with simvastatin can prevent this change without lowering the lipid levels,thus contributing to the ionic mechanism of simvastatin for antiarrhythmia.
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Objective To investigate the effects of pioglitazone on atrial ionic channel remodeling in alloxan-induced diabetic rabbit models.Methods A total of 32 rabbits were randomly (random number) divided into control (CN) group,diabetes mellitus (DM) group,diabetes mellitus + pioglitazone 4 mg/ (d · kg) (DPG) group and diabetes mellitus + double pioglitazone 8 mg/ (d · kg) (DPI) group.The diabetic state was examined by quantitative determination of blood glucose levels of ≥ 14 mmol/L.Langendorff-perfused rabbit hearts were used to isolate single atrial myocyte,and whole-cell patch-clamp technique was used to record action potential duration (APD) and atrial ionic channel currents (ICa,L and INa).Variables with normal distribution were compared with One-way ANOVA and LSD-t test.Results Compared with controls,APD90 and APDS0 of left atrial myocytes were significantly prolonged in DM group (P ＜0.05 vs.CN),and there was no significant difference in APD90 frequency adaptation between them (P ＞0.05 vs.CN).The densities of INa were reduced and the densities of ICa,L were increased in DM group (P ＜ 0.01 vs.CN).The above variables were markedly attenuated in DPG and DPI group.Conclusions Pioglitazone may inhibits atrial ionic channel remodeling in diabetic rabbit models.
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Objective: To study the effect of ghrelin on L-type calcium channel current (ICa-L) of ventricular myocytes in experimental rats. Methods: The single ventricular myocyte in experimental rats were obtained by enzymolysis method, and the whole-cell patch-clamp technique was used to investigate the effect of ghrelin on ICa-L of ventricular myocytes at different doses of 10 nmol/L, 100 nmol/L and 1μmol/L respectively. Results: Ghrelin at 10 nmol/L, 100 nmol/L and 1μmol/L may inhibit ICa-L at (8.95 ± 2.13) %, (31.18 ± 4.78) % and (64.63 ± 8.57)% respectively,P<0.05, and the current-voltage curve was shifted upwards. The channel half inactivation curve decreased from (-1.34 ± 1.9) mV to (-8.04 ± 1.32 ) mV, (9.76 ± 1.17) mV and (-11.81 ± 0.73) mV respectively,P<0.05, and the recovery time after inactivation was prolonged as τ value from (63.23 ± 9.32) to (98.95 ± 10.74), (109.56 ± 13.42) and (127.39 ± 16.13) respectively,P<0.05. Conclusion: Ghrelin may accelerate ICa-L inactivation and prolong the recovery time after inactivation. Ghrelin inhibits ICa-L in a dose-dependent manner.
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Sildenafil increases the cyclic guanosine monophosphate (cGMP) by inhibition of a phosphodiesterase 5, thereby leading to an antinociceptive effect. The increased cGMP may exert the effect on an L-type calcium channel through the activation of protein kinase G (PKG). The purpose of this study was to examine the possible involvement of a PKG-L-type calcium channel on the effect of sildenafil at the spinal level. Catheters were inserted into the intrathecal space of male SD rats. Pain was induced by applying 50 microliter of a 5% formalin solution to the hindpaw. The sildenafil-induced effect was examined after an intrathecal pretreatment of a PKG inhibitor (KT 5823), or a L-type calcium channel activator (FPL 64176). Intrathecal sildenafil produced an antinociceptive effect during phase 1 (0~10 min interval) and phase 2 (10~60 min interval) in the formalin test. Intrathecal KT 5823 and FPL 64176 attenuated the antinociceptive effect of sildenafil during both phases. Sildenafil is effective against both acute pain and the facilitated pain state at the spinal level. In addition, the inhibition of an L-type calcium channel by activation of the PKG may contribute to the antinocieptive mechanism of sildenafil in the spinal cord.
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Animals , Male , Rats , Calcium Channel Agonists/pharmacology , Calcium Channels, L-Type/physiology , Carbazoles/pharmacology , Cyclic GMP-Dependent Protein Kinases/antagonists & inhibitors , Dose-Response Relationship, Drug , Pain/drug therapy , Pain Measurement , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Purines/pharmacology , Pyrroles/pharmacology , Rats, Sprague-Dawley , Sulfones/pharmacologyABSTRACT
Objective To study the influence of arachidonic acid (AA) on L-type calcium channel in rabbits sin-gle cardiomyocyte and its mechanism of antiarrhythmia. Method The single ventricular cardiomyocyte was isolat-ed by using enzyme dispersion method and whole-cell clamp-patch technique was used to record L-type calcium current.All data were analyzed using ANOVA. Results AA inhibited Ica-L in a concentration-dependent manner. The application of 3 μmol/L, 10 μmol/L and 20 μmol/L arachidonic acid reduced the density of peak Ica-L from (10.79±0.93)pA/pF to (8.99±0.43)pA/pF to (7.60±0.35)pA/pF and to (5.60±0.30)pA/pF, respctive-ly (n=7, P<0. O1 ). The Ica-Lpartially resumed after washout. The AA up-shifted the I-V curves of Ica-L without changes of their shape,peak and reverse potentials. The AA also markedly shifted the inactivation curve to left, and prolonged the recorvery time from inactivation,but did not change the curve of calcium channel activation. Con-clustions By acceleration of L-type calcium channel inactivation and prolongation of recorvery time from inactiva-fion,arachidonic acid can reduce the calcium ion influe and prolong effective refractory period, playing the role of antiarrhythmia.
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Objective To investigate the effect of simvastatin on gene expression of L-type calcium channels(LCCs) of myocardial cells in BALB/c mice infected by coxsackievirus B3(CVB3) so as to study the therapeutic effect of simvastatin on viral myocarditis.Methods Sixty male BALB/c mice were divided into five groups randomly(n=12).Mice in viral control group and three groups of oral administration of simvastatin(10,30 and 90 mg?kg-1)were inoculated intrapritoneally with 0.2 mL of CVB3(Nancy strain).Mice in normal control group were inoculated intrapritoneally with 0.2 mL Eagle's solution.The heart samples of all the mice were obtained for hispathological study and detection of myocardial LCCs alpha1 subunits mRNA expression by semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR).Results In viral control group,the mononuclear inflamematory infiltrate was focal or diffuse in myocardium of mice,severe hearts revealed a large area of myocardial necrosis.The degree of inflammatory cell infiltrate and area of necrosis were significantly less in simvastatin groups as compared with viral control group.The myocardial LCCs alpha1 subunits mRNA expression by semi-quantitative RT-PCR in normal control group was much lower than that in viral control group(0.06?0.01 vs 1.37?0.32,P
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Objective To investigate the pathway and mechanism of neuropeptide Y(NPY)-Y1 receptor agonist,[Leu~(31),Pro~(34)]-NPY,on the cultured cerebrovascular smooth muscle cells(SMCs) in the spontaneously hypertensive rats(SHR) in vitro. Methods The SMCs of the arteries from the brain of SHR were cultured in vitro.Cell cycle was detected with flow cytometry,and the concentration of free intracellular calcium was examined with laser scanning confocal microscopy. Results The percentages of S stage cells of 10~(-5) mol/L and 10~(-6) mol/L NPY was higher than those of the control group(P
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In order to identify whether functional L-type calcium channels are expressed in neural stem cells(NSCs) from rat embryonic hippocampus, and whether L-type calcium channels participate in the modulation of proliferation and differentiation of NSCs, the rat embryonic hippocampal tissue was dispersed into a single cell suspension, and the dissociated cells were cultured in serum-free DMEM/F12 medium containing epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), N-2 and B27 supplement. Immunofluorescent labeling showed an expression of nestin-positive cells. Following five-days culture in differentiation medium, neuron-like and astrocyte-like cells were observed, which expressed ?-tubulin Ⅲ(Tuj1) and Glial fibrillary acidic protein (GFAP), respectively. Western blot analysis showed an expression of Cav1.2?1C subunits in NSCs, but no Cav1.3?1D subunits. Moreover, L-type calcium channel currents were recorded in those cells by using whole-cell patch clamp techniques. It was found that activation of L-type calcium channels promotes proliferation and differentiation to neuronal type of NSCs. The results indicated that rat embryonic hippocampal NSCs express functional L-type calcium channels, L-type calcium channels modulate proliferation and differentiation of NSCs.
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PURPOSE: This study was designed to investigate the effects of polyamines on rabbit seminal vesicular contractility. MATERIALS AND METHODS: The polyamines; putrescine, spermidine and spermine, were added to deepithelized and precontracted seminal vesicle strips, with either 10 4M norepinephrine (NE), 10 4M acetylcholine (ACh) or 70mM KCl, in organ chambers to obtain cumulative concentration response curves. A whole cell mode patch clamp study was also performed to observe the effects of the polyamines on the L-type calcium channel activities. RESULTS: The polyamines elicited concentration-dependent relaxations of the precontracted strips with the NE, ACh and KCl. The spermine showed the most potent relaxation response. Both extracellular and intracellular application of the spermine decreased the L-type calcium channel currents. CONCLUSIONS: Spermine more potently inhibited the seminal vesicle contraction than putrescine or spermidine, which suggests the polyamines may play a role in maintaining the basal tonicity of seminal vesicle in a flaccid state. The spermine-induced relaxation response seems to be related with an inhibition of the L-type calcium channel activities.
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Acetylcholine , Calcium Channels, L-Type , Norepinephrine , Polyamines , Putrescine , Relaxation , Seminal Vesicles , Spermidine , SpermineABSTRACT
Objective: To investigate the action of tetramethylpyrazines on cardiac myocyte hypertrophy induced by endothelin-1(ET-1). Methods: The blockers of L-type calcium channel(Larcidipine),TMPP and TMPH were used to influence protein synthesis stimulated by chronic ET-1. Results:(ET-1) group's intracellular protein content in cardiac myocyte was(279?39)?g/ml(17% higher than the control group,P
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Aim To investigate the effects of L-type calcium channel blockers on tramadol-induced analgesia.Methods Hot-plate test and writhing test were used to measure the analgesia induced by tramadol. Verapamil, nimodipine or nifedipine was co-administrated with tramadol to determine its effects on tramadol analgesia.Results Tramadol (10, 20, 40 mg?kg -1 in hot-plate test or 2, 5,10 mg?kg -1 in writhing test) produced significantly analgesia in hot-plate test and writhing test. Co-administration of verapamil and tramadol prolonged the latency of pain response of mice in hot-plate test.In writhing test, verapamil, nimodipine and nifedipine could potentiate the analgesic effect of tramadol in a dose-dependent manner.Conclusion L-type calcium channel blockers can potentiate tramadol-induced analgesia. Calcium influx mediated by L-type calcium channels may be involved in tramadol-induced analgesia.