目的利用在体大鼠心肌缺血再灌注模型观察Bayk8644对大鼠心功能的影响。方法将18只大鼠随机分为3组:假手术组(sham组)、Bay k8644组(B组)和二甲基亚枫组(D组),分别在缺血30 m in时静脉持续泵入生理盐水、Bay k8644和二甲基亚枫,于缺血前...目的利用在体大鼠心肌缺血再灌注模型观察Bayk8644对大鼠心功能的影响。方法将18只大鼠随机分为3组:假手术组(sham组)、Bay k8644组(B组)和二甲基亚枫组(D组),分别在缺血30 m in时静脉持续泵入生理盐水、Bay k8644和二甲基亚枫,于缺血前,缺血5、20、40 m in以及再灌注5、30、60、90 m in时,分别测定心率(HR)、左心室收缩峰压(LVSP)、左心室舒张末压(LVEDP)、左心室压力变化最大速率(±dp/dtm ax),以评价心脏功能。结果缺血后HR变化不显著,LVSP和+dp/dtm ax降低(与缺血前和sham组比较差异有显著性P<0.05),LVEDP升高,-dp/dtm ax降低;再灌注时B组HR逐渐减慢,D组逐渐增快,两组比较差异无显著性(P>0.05);LVSP和+dp/dtm ax进行性升高,LVEDP升高,-dp/dtm ax降低,各时间点两组比较差异无显著性(P>0.05)。结论持续静脉注射Bay k8644(2μg.kg-1.m in-1)不影响缺血再灌注损伤大鼠的心脏功能。展开更多
Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus ...Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.展开更多
Binding of La3+ to Fura-2 can change 340/380 nm fluorescence intensity ratio. Whether La3+ cross ventricular cell membrane was detected by this fluorescent probe technique. Fura-2 loaded isolated guinea pig ventricula...Binding of La3+ to Fura-2 can change 340/380 nm fluorescence intensity ratio. Whether La3+ cross ventricular cell membrane was detected by this fluorescent probe technique. Fura-2 loaded isolated guinea pig ventricular cells were exposed to 0.01-0.1 mM extracellular Lanthanum ion concentration, 340nm/380 nm fluorescence ratio was not changed. Using calcium channel agonist BAY K8644, KCL (35mM) depolarization to open the voltage-dependent calcium channel (VDCC); Adrenoceptor agonist to excite adrenoceptor, 340/380 ratio was not changed, suggesting that La3+can not enter guinea pig ventricular cells in this case.展开更多
目的:观察硫化氢(H2S)对家兔肠系膜血管环张力的调节作用,及其可能的作用机制。方法:应用离体血管环张力测定技术,用金属钩将3mm左右的动脉环悬置于含K-H液的离体器官浴槽中,观察硫化氢在血管环张力的作用,由计算机生物信号采集处理系...目的:观察硫化氢(H2S)对家兔肠系膜血管环张力的调节作用,及其可能的作用机制。方法:应用离体血管环张力测定技术,用金属钩将3mm左右的动脉环悬置于含K-H液的离体器官浴槽中,观察硫化氢在血管环张力的作用,由计算机生物信号采集处理系统进行记录分析,检测血管环张力的变化,制作浓度反应曲线。结果:(1)外源性的NaHS(H2S的供体)可以剂量依赖性地舒张由氯化钾(KCL)预收缩的肠系膜动脉血管环。(2)用ATP敏感性钾通道(KA T P)通道阻断剂格列苯脲(Gli)、钙通道的开放剂1,4-二氢-2,6-二甲基-5-硝基-4-(2-[三氟甲基]苯基)吡啶-3-羧酸甲酯(Bay K8644)、NO合酶的抑制剂左旋硝基精氨酸甲酯(L-NAME)和环氧合酶阻断剂吲哚美辛预处理以及去除血管内皮后,H2S的舒张效应均被显著抑制,浓度反应曲线均明显右移。(3)给予鸟苷酸环化酶的抑制剂1H-(1,2,4)恶二唑(4,3-α)喹喔啉-1-酮(ODQ)预处理后,对H2S的舒张作用没有显著改变。结论:H2S在50～800μmol/L之间浓度依赖性的舒张家兔肠系膜动脉,部分是通过开放KA T P通道和关闭L型钙通道实现的,但与3ˊ,5ˊ-环一磷酸鸟苷(cGMP)途径无关。此作用是内皮依赖性的,且与一氧化氮(NO)和前列环素(PGI2)具有协同作用。展开更多
The distribution of the immediate early gene c-fos expression in the mouse central nervous system after subcutaneous injection of Bay K 8644 was observed immunohistochemically. Half an hour after injection, cfos prote...The distribution of the immediate early gene c-fos expression in the mouse central nervous system after subcutaneous injection of Bay K 8644 was observed immunohistochemically. Half an hour after injection, cfos protein (FOS) was expressed in the piriform cortex, sensorimotor cortex, caudate putamen, thalamic paraventricular nucleus and striate cortex,etc. Intense FOS immunoreactive (FOS-ir) cells were seen during 2 ～ 4 h after injection. The restllts suggested that the distribution of FOS-ir ce1ls after subcutaneous injection of Bay K 8644 was coincldent with that of L-type calcium channels in the different areas of the CNS. After Bay K 8644 injection, mice appeared seizure-like behavior. The percentage of cells double-labelled by FOS and CaBP immunoreactivities in the observed regions was about 60. 2～72. 8% in CaBP-ir cells. It suggested that most CaBP-lr cells may have L-type calcium channels.展开更多
Background It has been reported that hydrogen sulfide （H2S） could relax vascular smooth muscle by direct activation of KATP channels and hyperpolarization of the membrane potential. Recently, our study has shown tha...Background It has been reported that hydrogen sulfide （H2S） could relax vascular smooth muscle by direct activation of KATP channels and hyperpolarization of the membrane potential. Recently, our study has shown that H2S facilitated carotid baroreflex. This study was conducted to investigate the effect of H2S on carotid baroreceptor activity （CBA）. Methods The functional curve of carotid baroreceptor （FCCB） was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Results H2S （derived from NariS） 25, 50 and 100 pmol/L facilitated CBA, which shifted FCCB to the left and upward. There was a marked increase in peak slope （PS） and peak integral value of carotid sinus nerve charge （PIV） in a concentration-dependent manner. Pretreatment with glibenclamide （20 pmol/L）, a KATP channel blocker, the above effects of H2S on CBA were abolished. Pretreatment with Bay K8644 （an agonist of calcium channels, 500 nmol/L） eliminated the role of H2S on CBA. An inhibitor of cystathionine y-lyase （CSE）, DL-propargylglycine （PPG, 200 pmol/L） inhibited CBA in male rats and shifted FCCB to the right and downward. Conclusions Our results suggest that exogenous H2S exerts a facilitatory role on isolated CBA through opening KATP channels and further closing the calcium channels in vascular smooth muscle. Endogenous H2S may activate CBA in vivo.展开更多
基金The project supported by Foundation ofScience &Technology Bureau of Hebei Province(062761773)Natural Science Foundation of Education Bureau of Hebei Province(Z2006110)~~
文摘Objective To study the central role of ginkgolide B （BN52021） in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus （PVN） neurons in hypothalamic slice preparation and to elucidate the mechanism involved. Methods Extracellular single-unit discharge recording technique. Results （1） In response to the application of ginkgolide t3 （0.1, 1, 10 μmol/L; n = 27） into the perfusate for 2 rain, the spontaneous discharge rates （SDR） of 26 （26/27, 96.30%） neurons were significantly decreased in a dose-dependent manner. （2） Pretreatment with L-glutamate （L-Glu, 0.2 mmol/L） led to a marked increase in the SDR of all 8 （100%） neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B （1 μmol/L） was applied into the perfusate for 2 min. （3） In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 （0.1 μmol/L）, induced a significant increase in the discharge rates of 8 （8/8, 100%） neurons, while ginkgolide B （1μmol/L） applied into the perfusate, could inhibit the discharges of 8 （100%） neurons. （4） In 8 neurons, the broad potassium channels blocker, tetraethylammonium （TEA, 1 mmol/L） completely blocked the inhibitory effect of ginkgolide B （1 μmol/L）. Conclusion These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel （KDR）.
文摘Binding of La3+ to Fura-2 can change 340/380 nm fluorescence intensity ratio. Whether La3+ cross ventricular cell membrane was detected by this fluorescent probe technique. Fura-2 loaded isolated guinea pig ventricular cells were exposed to 0.01-0.1 mM extracellular Lanthanum ion concentration, 340nm/380 nm fluorescence ratio was not changed. Using calcium channel agonist BAY K8644, KCL (35mM) depolarization to open the voltage-dependent calcium channel (VDCC); Adrenoceptor agonist to excite adrenoceptor, 340/380 ratio was not changed, suggesting that La3+can not enter guinea pig ventricular cells in this case.
文摘目的:观察硫化氢(H2S)对家兔肠系膜血管环张力的调节作用,及其可能的作用机制。方法:应用离体血管环张力测定技术,用金属钩将3mm左右的动脉环悬置于含K-H液的离体器官浴槽中,观察硫化氢在血管环张力的作用,由计算机生物信号采集处理系统进行记录分析,检测血管环张力的变化,制作浓度反应曲线。结果:(1)外源性的NaHS(H2S的供体)可以剂量依赖性地舒张由氯化钾(KCL)预收缩的肠系膜动脉血管环。(2)用ATP敏感性钾通道(KA T P)通道阻断剂格列苯脲(Gli)、钙通道的开放剂1,4-二氢-2,6-二甲基-5-硝基-4-(2-[三氟甲基]苯基)吡啶-3-羧酸甲酯(Bay K8644)、NO合酶的抑制剂左旋硝基精氨酸甲酯(L-NAME)和环氧合酶阻断剂吲哚美辛预处理以及去除血管内皮后,H2S的舒张效应均被显著抑制,浓度反应曲线均明显右移。(3)给予鸟苷酸环化酶的抑制剂1H-(1,2,4)恶二唑(4,3-α)喹喔啉-1-酮(ODQ)预处理后,对H2S的舒张作用没有显著改变。结论:H2S在50～800μmol/L之间浓度依赖性的舒张家兔肠系膜动脉,部分是通过开放KA T P通道和关闭L型钙通道实现的,但与3ˊ,5ˊ-环一磷酸鸟苷(cGMP)途径无关。此作用是内皮依赖性的,且与一氧化氮(NO)和前列环素(PGI2)具有协同作用。
文摘The distribution of the immediate early gene c-fos expression in the mouse central nervous system after subcutaneous injection of Bay K 8644 was observed immunohistochemically. Half an hour after injection, cfos protein (FOS) was expressed in the piriform cortex, sensorimotor cortex, caudate putamen, thalamic paraventricular nucleus and striate cortex,etc. Intense FOS immunoreactive (FOS-ir) cells were seen during 2 ～ 4 h after injection. The restllts suggested that the distribution of FOS-ir ce1ls after subcutaneous injection of Bay K 8644 was coincldent with that of L-type calcium channels in the different areas of the CNS. After Bay K 8644 injection, mice appeared seizure-like behavior. The percentage of cells double-labelled by FOS and CaBP immunoreactivities in the observed regions was about 60. 2～72. 8% in CaBP-ir cells. It suggested that most CaBP-lr cells may have L-type calcium channels.
基金国家自然科学基金，河南省卫生厅科技创新型人才工程“中青年科技创新人才”(4105)Fund program:National Natural Science Foundation of China，Innovation Talents of Science and Technology for the Department of Health Science and Technology Innovation Talents Project,Youth Program in Henan Province
基金the Natural Science Foundation of Hebei Province of China(No.C2007000821)
文摘Background It has been reported that hydrogen sulfide （H2S） could relax vascular smooth muscle by direct activation of KATP channels and hyperpolarization of the membrane potential. Recently, our study has shown that H2S facilitated carotid baroreflex. This study was conducted to investigate the effect of H2S on carotid baroreceptor activity （CBA）. Methods The functional curve of carotid baroreceptor （FCCB） was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus. Results H2S （derived from NariS） 25, 50 and 100 pmol/L facilitated CBA, which shifted FCCB to the left and upward. There was a marked increase in peak slope （PS） and peak integral value of carotid sinus nerve charge （PIV） in a concentration-dependent manner. Pretreatment with glibenclamide （20 pmol/L）, a KATP channel blocker, the above effects of H2S on CBA were abolished. Pretreatment with Bay K8644 （an agonist of calcium channels, 500 nmol/L） eliminated the role of H2S on CBA. An inhibitor of cystathionine y-lyase （CSE）, DL-propargylglycine （PPG, 200 pmol/L） inhibited CBA in male rats and shifted FCCB to the right and downward. Conclusions Our results suggest that exogenous H2S exerts a facilitatory role on isolated CBA through opening KATP channels and further closing the calcium channels in vascular smooth muscle. Endogenous H2S may activate CBA in vivo.
