胍丁胺对异丙肾上腺素诱发豚鼠乳头状肌后除极的影响(英文)

目的:研究胍丁胺(Agm)对异丙肾上腺素(Iso)诱发豚鼠乳头状肌早发和晚发后除极(EAD和DAD)的影响及其作用机制。方法:细胞内玻璃微电极技术。结果:(1)Agm明显抑制Iso诱发的EAD和DAD;(2)预先应用NOS抑制剂L-NAME0.5mmol·L~(-1),不能影响Agm1.0mmol·L~(-1)对Iso 20nmol·L~(-1)诱发EAD和DAD的抑制作用;(3)预先应用咪唑啉受体(IR)和肾上腺素能α_2受体(α_2-AR)拮抗剂idazoxan 0.1mmol·L~(-1)则可阻断这种作用。结论:Agm对Iso诱发EAD和DAD的抑制作用由α_2-AR和/或IR介导,并与钙内流减少有关。     

胍丁胺对异丙肾上腺素诱发人心房纤维迟后除极的影响(英文)

用标准微电极技术研究胍丁胺对异丙肾上腺素 ( Iso)诱发人心房纤维迟后除极的影响 .结果如下 :( 1 )胍丁胺 ( 1 - 1 0 mmol· L-1)以浓度依赖地方式明显抑制 Iso( 2 0 nmol· L-1)诱发人心房纤维的迟后除极 ;( 2 )预先应用咪唑啉受体和 α2 肾上腺素受体拮抗剂咪唑克生 ( 0 .1 mmol· L-1)可阻断胍丁胺 ( 1 0 mmol· L-1)对 Iso( 2 0 nmol· L-1)诱发迟后除极的抑制作用 ;( 3)预先应用一氧化氮合酶抑制剂硝基 - L-精氨酸甲酯 ( 0 .5mmol· L-1) ,不影响胍丁胺 ( 1 0 mmol· L-1)对 Iso( 2 0 nmol· L-1)诱发迟后除极的抑制作用 .结果表明 ,胍丁胺对 Iso诱发人心房纤维迟后除极的抑制作用可能是由于咪唑啉受体和 α2 肾上腺素受体介导钙内流减少所致 .     

胍丁胺对异丙肾上腺素诱发人心房纤维迟后除极的影响

用标准微电极技术研究胍丁胺对异丙肾上腺素 (Iso) 诱发人心房纤维迟后除极的影响. 结果如下：(1) 胍丁胺 (1-10 mmol·L^-1)以浓度依赖地方式明显抑制Iso (20 nmol·L^-1) 诱发人心房纤维的迟后除极;(2) 预先应用咪唑啉受体和α₂肾上腺素受体拮抗剂咪唑克生(0.1 mmol·L^-1) 可阻断胍丁胺 (10 mmol·L^-1) 对Iso(20 nmol·L^-1)诱发迟后除极的抑制作用;(3) 预先应用一氧化氮合酶抑制剂硝基-L-精氨酸甲酯(0.5 mmol·L^-1),不影响胍丁胺 (10 mmol·L^-1) 对Iso(20 nmol·L^-1)诱发迟后除极的抑制作用. 结果表明,胍丁胺对Iso诱发人心房纤维迟后除极的抑制作用可能是由于咪唑啉受体和α₂肾上腺素受体介导钙内流减少所致.     

17β-雌二醇抑制麻醉雄性大鼠颈动脉窦压力感受器的活动(英文)

目的:观察17β-雌二醇对颈动脉窦压力感受器活动的影响。方法:在麻醉雄性大鼠隔离灌流颈动脉窦条件下记录窦神经传入放电,观察17β-雌二醇(E_2)对压力感受器机能曲线和机能参数的影响。结果:E_23,10和30μmol/L使压力感受器机能曲线向右下方移位,曲线最大斜率和窦神经传入放电积分最大值均明显减小,表明E_2可抑制颈动脉窦压力感受器活动。雌激素受体抑制剂他莫昔芬10μmol/L不能阻断E_2的效应。一氧化氮合酶阻断剂L-NAME100μmol/L完全阻断E_2对压力感受器活动的抑制效应。一氧化氮供体SIN-1 10μmol/L能加强E_2的效应。结论:E_2抑制雄性大鼠颈动脉窦压力感受器的活动,此效应系其使内皮细胞释放一氧化氮所致。     

咪唑啉结合位点及受体与心血管功能

人及大鼠心肌细胞存在 2 型咪唑啉结合位点 ,多种动物的血管平滑肌存在 1 型和 2 型咪唑啉结合位点 ,其中 2 型咪唑啉结合位点可能参与血管平滑肌的增殖。支配心血管系统的交感神经末梢存在突触前咪唑啉受体 ,激动该受体抑制NE的释放。与多数咪唑啉类化合物不同 ,莫索尼定对突触前咪唑啉受体无效 ,而大麻受体拮抗剂SR141716A对该受体具有拮抗作用。已经证实多数咪唑啉类化合物具有抗心律失常作用 ;咪唑啉受体的内源性配基胍丁胺降低动物窦房结起搏细胞的放电频率 ,延长人与动物心肌细胞的动作电位时程 ,对异丙肾上腺素诱发的后除极具有抑制作用。但是 ,咪唑啉类和胍类化合物非竞争性抑制心血管系统的KATP通道 ,可能干扰IK .ATP的心脏保护作用。     

莫索尼定对麻醉大鼠颈动脉窦压力感受器反射的影响

目的:观察莫索尼定对颈动脉窦压力感受器反射的影响。方法:利用灌流左颈动脉窦方法,观察莫索尼定对麻醉大鼠压力反射机能参数的影响。恒流灌流股动脉,记录灌流压变化,确定莫索尼定对血管阻力的影响。结果:莫索尼定32,100μmol·L~(-1)使颈动脉窦压力反射机能曲线向右上移位,曲线最大斜率和反射性平均动脉压下降幅度均减小,提示莫索尼定对压力感受器反射有抑制作用。伊法克生100μmol·L~(-1)完全阻断莫索尼定100μmol·L~(-1)的效应。莫索尼定显著增加血管阻力。结论:莫索尼定对颈动脉窦压力反射有直接抑制作用,此作用可能在于其引起窦壁收缩所致。     

八肽胆囊收缩素对大鼠颈动脉窦神经传入放电的抑制作用(英文)

目的　观察八肽胆囊收缩素 (CCK 8)是否通过直接抑制颈动脉窦压力感受器放电活动而影响心血管功能。方法　在麻醉雄性大鼠隔离灌流颈动脉窦区条件下记录窦神经传入放电及积分。结果　①CCK 80 .1,0 .5和 1.0 μmol·L- 1使压力感受器机能曲线向右下方移位 ,曲线最大斜率和窦神经传入放电积分最大值均明显减小 ,表明CCK 8可剂量依赖性抑制颈动脉窦压力感受器活动。②预先灌流CCK 8非特异性受体阻断剂丙谷胺 10 0 μmol·L- 1或钙通道开放剂BayK86 440 .5 μmol·L- 1可部分阻断CCK 80 .5 μmol·L- 1对颈动脉窦压力感受器放电活动的抑制作用。预先灌流一氧化氮合酶抑制剂L NAME不能阻断CCK 8的效应。结论　CCK 8可直接抑制大鼠颈动脉窦压力感受器传入神经放电活动。其机制可能为CCK 8作用于颈动脉窦区相应的受体后 ,对牵张敏感性通道产生抑制作用。     

白藜芦醇抑制麻醉大鼠颈动脉窦压力感受性反射(英文)

目的研究白藜芦醇的心血管保护作用是否与其对颈动脉窦压力感受器的作用有关。方法隔离灌流麻醉大鼠颈动脉窦区,同时记录动脉血压的变化,并绘制压力感受性反射的功能曲线。结果白藜芦醇(30,60和120μmol.L-1)隔离灌流颈动脉窦区,压力感受性反射机能曲线向右上方移位,曲线的最大斜率下降,反射性血压下降的幅度降低,阈压增加,其变化呈浓度依赖性。预先应用NO合酶抑制剂L-NAME100μmo.lL-1或钙通道开放剂BayK8644500nmol.L-1可消除白藜芦醇对压力感受器的抑制作用。用酪氨酸磷酸酶抑制剂正钒酸钠1mmol.L-1预处理对白藜芦醇抑制压力感受性反射的作用无影响。结论白藜芦醇对大鼠颈动脉窦压力感受器反射有抑制作用,此作用可能与局部NO的释放及减弱牵张敏感性通道的钙离子内流有关。     

胍丁胺对炎性疼痛的镇痛作用及对吗啡镇痛作用的影响

目的观察胍丁胺对炎性疼痛的镇痛作用及其对吗啡镇痛作用的影响,研究胍丁胺的镇痛作用是否与激动咪唑啉受体或影响受体前谷氨酸和γ-氨基丁酸(gamma-aminobutyr-icacid,GABA)释放有关。方法应用福尔马林致大鼠炎性疼痛模型,观察胍丁胺镇痛和增强吗啡镇痛的作用。应用高效液相色谱技术测定胍丁胺对脊髓切片孵育液中谷氨酸和GABA基础释放量及对高钾诱发神经元去极化引起神经递质释放的影响。结果单侧足底注射5%福尔马林使大鼠出现明显的双相伤害性行为反应。胍丁胺抑制福尔马林引起的第二相疼痛行为反应及痛觉过敏,并增强吗啡对第二相疼痛的镇痛作用,但在第一相疼痛过程中,无明显镇痛和增强吗啡镇痛的作用。咪唑啉受体拮抗剂咪唑克生不能拮抗胍丁胺镇痛及增强吗啡镇痛的作用。1~1000μmol.L-1胍丁胺对脊髓谷氨酸和GABA的基础释放量和高钾诱发谷氨酸和GABA释放量的升高均没有影响。结论胍丁胺对炎性疼痛具有明确的镇痛作用,并明显增强吗啡的镇痛效果,其镇痛机制可能与咪唑啉受体无关,也不是通过在受体前水平抑制谷氨酸或促进GABA释放来实现的。     

利用RNA干扰技术研究I1咪唑啉受体在阿片依赖中的作用

目的：我们和国外实验室先后研究发现胍丁胺对阿片依赖具有调节作用，其作用可能与I1咪唑啉受体（I1-imidazoline receptor，I1R）有关。但由于没有特异性咪唑啉受体拮抗剂且胍丁胺的作用靶点较多，到目前为止，I1R是否为胍丁胺抗阿片依赖的主要作用靶点尚不能完全确定。因此，本文旨在利用RNA干扰技术确定I1R是否介导胍丁按对阿片依赖的调节作用。方法：利用RNA干扰技术下调细胞内源性I1R的表达，     

胍丁胺对异丙肾上腺素诱发豚鼠乳头状肌后除极的影响

AIM: To study the effects of agmatine (Agm) on early afterdepolarizations (EAD) and delayed afterdepolarizations (DAD) induced by isoproterenol (Iso) in guinea pig papillary muscles. METHODS: EAD and DAD were recorded using intracellular glass microelectrode technique. RESULTS: (1) EAD and DAD induced by Iso 20 nmol.L-1 were markedly inhibited by pretreatment with Agm 1.0-2.0 mmol.L-1 in a concentration-dependent manner. (2) NG-nitro-L-arginine methyl ester (L-NAME, 0.5 mmol.L-1), a NOS inhibitor, did not affect the inhibitory effects of Agm (1.0 mmol.L-1) on EAD and DAD induced by Iso. (3) The inhibitory effects of Agm (1.0 mmol.L-1) on EAD and DAD induced by Iso (20 nmol.L-1) were eliminated by pretreatment with idazoxan (Ida, 0.1 mmol.L-1), an alpha-2 adrenergic receptor (alpha 2-AR) and imidazoline receptor (IR) antagonist. CONCLUSION: The inhibitory effects of Agm on EAD and DAD induced by Iso in papillary muscles is related to the reduction in calcium influx and mediated by alpha 2-AR and/or IR.     

Urotensin Ⅱ inhibits carotid sinus baroreflex in anesthetized male rats

AIM: To study the effects of urotensin II (UII) on the carotid sinus baroreflex (CSB). METHODS: The functional curve of carotid sinus baroreflex was measured by recording changes in arterial pressure in anesthetized male rats with perfused isolated carotid sinus. RESULTS: UII at the concentration of 3 nmol/L had no effect on the CSB, while at the concentration of 30, 300 and 3000 nmol/L inhibited the CSB, shifting the functional curve of the baroreflex upward and to the right. There was a marked decrease in peak slope and reflex decrease in blood pressure. These effects of UII were concentration-dependent. Pretreatment with verapamil (an antagonist of the L-type calcium channel, 10 micromol/L) partially eliminated the above effects of UII (300 nmol/L) on the CSB. Pretreatment with BIM-23127 (3 micromol/L), an antagonist of human and rat UII receptors, abolished the actions of UII on the CSB. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) 100 micromol/L did not affect the inhibitory effects of UII (300 nmol/L) on the CSB. CONCLUSION: These data suggest that UII exerts an inhibitory action on the isolated CSB. Such an action of UII is predominantly mediated by the UII receptors in vascular smooth muscles, resulting in the opening of L-type calcium channels.     

胍丁胺对兔窦房结起搏细胞的电生理效应

AIM: To study the electrophysiologic effects of agmatine (Agm) on pacemaker cells in sinoatrial (SA) node. METHODS: Parameters of action potential (AP) in SA node were recorded using intracellular microelectrode technique. RESULTS: Agm not only slowed down the amplitude of action potential (APA), maximal rate of depolarization (Vmax), velocity of diastolic (phase 4) depolarization (VDD), and rate of pacemaker firing (RPF), but also prolonged 90% duration of action potential (APD90) in a concentration-dependent manner. The effects of Agm (10 mmol.L-1) could be blocked completely by pretreatment with idazoxan (0.15 mmol.L-1), an alpha 2-adrenergic receptor (alpha 2-AR) and imidazoline receptor (IR) antagonist. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 1 mmol.L-1), an NOS inhibitor, did not affect the electrophysiologic effects of Agm on pacemaker cells in SA node. Elevation of Ca2+ concentration (5 mmol.L-1) in perfusate antagonized the effects of Agm (10 mmol.L-1). Lemakalim (Lem, 30 mumol.L-1), an opener of ATP-sensitive potassium channels, partially inhibited the prolonging effect of Agm on repolarization. CONCLUSION: The electrophysiologic effects of Agm on pacemaker cells in SA node were likely attributed to the reduction in calcium influx and potassium efflux and mediated by alpha 2-AR and IR.     

胍丁胺抑制兔房室结细胞的自发活动(英文)

目的:研究胍丁胺(Agm)对兔房室结细胞自发活动的影响及其作用机制.方法:应用玻璃微电极方法.结果:Agm不仅剂量依赖地抑制兔房室结细胞自发活动的V_(max),APA和VDD,RSF;而且延长APD_(90);idazoxan能明显抑制Agm的作用;而L-NAME不能影响Agm的作用;提高灌流液中的Ca~(2 )浓度可对抗Agm的作用;ATP-敏感性钾通道开放剂(lemakalim)可拮抗Agm延长APD_(90)的作用.结论:Agm对房室结细胞自发活动的抑制作用由咪唑啉受体和/或肾上腺素α_2-受体介导,并与Ca~(2 )内流和K~ 外流减少有关.     

Hydrogen sulfide facilitates carotid sinus baroreflex in anesthetized rats

AIM: To study effects of hydrogen sulfide (H2S) on the carotid sinus baroreflex (CSB). METHODS: The functional curve of the carotid sinus baroreflex was measured by recording changes in arterial pressure in anesthetized male rats with perfused carotid sinus. RESULTS: H2S (derived from sodium hydrosulfide) at concentrations of 25, 50, and 100 micromol/L facilitated the CSB, shifting the functional curve of the baroreflex downward and to the left. There was a marked increase in peak slope (PS) and reflex decrease in blood pressure (RD). Effects were concentration-dependent. Pretreatment with glibenclamide (20 micromol/L), a K(ATP) channel blocker, abolished the above effects of H2S on CSB. Pretreatment with Bay K8644 (an agonist of calcium channels; 500 nmol/L) eliminated the effect of H2S on CSB. An inhibitor of cystathionine gamma-lyase (CSE), DL-propargylglycine (PPG; 200 micromol/L), inhibited CSB in male rats and shifted the functional curve of the baroreflex upward and to the right. CONCLUSION: These data suggest that exogenous H2S exerts a facilitatory role on isolated CSB through opening K(ATP) channels and further closing the calcium channels in vascular smooth muscle. Endogenous H2S may activate the activity of the CSB in vivo.     

Genistein inhibits carotid sinus baroreceptor activity in anesthetized male rats

Aim: To study the effect of genistein (GST) 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: GST at 50, 100, and 200 μmol/L inhibited the CBA, which shifted FCCB to the right and downward, with a marked decrease in peak slope and peak integral value of carotid sinus nerve discharge in a concentration-dependent manner. Pretreatment with 100 μmol/L N^G-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, did not affect the effect of GST on CBA. Pretreatment with 500 nmol/L Bay K8644, an agonist of calcium channels, could completely abolish the effect of GST on CBA. A potent inhibitor of tyrosine phosphatase, sodium orthovanadate (1 mmol/L), could attenuate the inhibitory effect of GST. Conclusion: GST inhibits CBA, and the effect may be mediated by protein tyrosine kinase inhibition and a decrease in Ca^2 influx through the stretchactivated channels.     

17 beta-Estradiol inhibits carotid sinus baroreceptor activity in anesthetized male rats.

AIM: To study the effect of 17beta-estradiol (E2) 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: E2 3, 10, and 30 micromol/L shifted FCCB to the right and downward, with a marked decrease in peak slope (PS) and peak integral value of carotid sinus nerve discharge (PIV) in a concentration-dependent manner, indicating the inhibitory effect of E2 on CBA. Pretreatment with tamoxifen (TAM) 10 micromol/L, an inhibitor of estrogen receptor, did not block the effect of E2 on CBA. Preperfusion with L-NAME 100 micromol/L, an inhibitor of NO synthase, could completely abolish the effect of E2 on CBA. NO donor SIN-1 10 micromol/L could potentiate the inhibitory effect of E2. CONCLUSION: E2 inhibits CBA via endothelial NO release.     

Capsaicin facilitates carotid sinus baroreceptor activity in anesthetized rats

AIM: To study the effect of capsaicin on carotid sinus baroreceptor activity (CBA). METHODS: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid sinus baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized rats with perfused isolated carotid sinus. RESULTS: Low-concentration of capsaicin (0.2 μmol/L) had no significant effect on CBA, while perfusion of the isolated carotid sinus with middle-concentration of capsaicin (1 μmol/L) could shift FCCB to the left and upward, with peak slope (PS) increased from (2.47 %±0.14 %)/mmHg to (2.88 %±0.10 %)/mmHg (P<0.05) and peak integral value of carotid sinus nerve discharge (PIV) enhanced from 211 %±5 % to 238 %±6 % (P<0.01). The threshold pressure (TP) and saturation pressure (SP) were significantly decreased from 68.0±1.1 to 62.7±1.0 mmHg (P<0.01) and from 171.0±1.6 to 165.0±0.6 mmHg (P<0.01). By perfusing with high-concentration of capsaicin (5μmol/L), FCCB was shi     

莫索尼定对麻醉大鼠颈动脉窦压力感受器反射的影响

观察莫索尼对颈动脉窦压力感受器反射的影响。方法：利用灌流左颈动脉窦方法，观察莫索尼定对麻醉大鼠压力反射机能参数的影响。恒流灌流股动脉，记录灌流压变化，确定莫索尼定对血管阻力的影响。结果；莫索尼定３２．１００μｍｏｌ．Ｌ＾－１使颈动脉窦压力反射机能曲线向右上移位，曲线最大斜率和反射性平均动脉压下降幅度均减小，提示莫索尼定对压力感受器反射有抑制作用。     

白藜芦醇对麻醉大鼠颈动脉窦压力感受器的作用

在隔离灌流左侧颈动脉窦区的麻醉大鼠上观察了白藜芦醇对颈动脉窦压力感受器活动的影响。隔离灌流麻醉大鼠的颈动脉窦区，同时记录窦神经放电，并绘制压力感受器活动的机能曲线。白藜芦醇(30， 60及120 μmol·L^-1)隔离灌流颈动脉窦区时，压力感受器活动的机能曲线向右下方移位，曲线的斜率以及窦神经放电的最大积分值显著下降，且其变化呈一定的剂量依赖性。预先应用NO合酶抑制剂(L-NAME， 100 μmol·L^-1)可完全消除白藜芦醇对压力感受器活动的抑制作用；预先应用钙通道的开放剂(Bay K8644， 500 nmol·L^-1)可以取消白藜芦醇的抑制作用；预先应用正矾酸钠(sodium orthovanadate， 1 mmol·L^-1)后，对白藜芦醇抑制压力感受器活动的作用无影响。白藜芦醇对大鼠颈动脉窦压力感受器活动有抑制作用，此作用可能与局部NO的释放及减弱牵张敏感性通道介导的钙离子内流有关。