心肌缺血对心肌去甲肾上腺素的释放

去甲肾上腺素（ＮＥ）在心肌缺血病理过程中起重要作用，本文综述了心肌缺血不同时期心肌ＮＥ释放规律及药物、心肌代谢产物对其释放的影响。     

Calpain 1在黄芪甲苷抑制异丙肾上腺素诱导的大鼠心肌凋亡中的作用

目的探讨Calpain 1在黄芪甲苷抑制异丙肾上腺素诱导的大鼠心肌凋亡中的作用。方法 SD大鼠48只,随机分为6组,每组8只:正常对照组、异丙肾上腺素组、异丙肾上腺素+普萘洛尔40 mg/(kg·d)组、异丙肾上腺素+黄芪甲苷20 mg/(kg·d)组、异丙肾上腺素+黄芪甲苷40 mg/(kg·d)组、异丙肾上腺素+黄芪甲苷80mg/(kg·d)组。给药组连续灌胃2周,并于灌胃1天后腹腔注射异丙肾上腺素10 mg/(kg·d)2周。2周后,采用TUNEL检测心肌凋亡,电镜观察心肌线粒体病变,Western blot检测心肌线粒体Calpain 1、凋亡诱导因子(AIF)的蛋白表达和心肌组织多聚ADP核糖聚合酶1(PARP1)的蛋白表达。结果与正常对照组相比,异丙肾上腺素组凋亡率明显增加;心肌线粒体肿胀、膜融合消失、嵴断裂;心肌线粒体中Calpain 1表达增加,AIF表达减少;心肌组织中PARP1表达增加。与异丙肾上腺素组相比,异丙肾上腺素+黄芪甲苷40 mg/(kg·d)组、异丙肾上腺素+80mg/(kg·d)组表现为心肌凋亡率减少;心肌线粒体结构相对完整;心肌线粒体Calpain 1表达减少,AIF表达增加;心肌组织PARP1表达减少,且呈一定的剂量依赖性。结论黄芪甲苷对异丙肾上腺素诱导的心肌凋亡有一定的保护作用,其机制可能与抑制线粒体Calpain 1表达,从而减少线粒体AIF释放至胞浆并转位至核有关。     

血液透析对细胞内游离钙和细胞膜β肾上腺素能受体密度的影响

本研究旨在观察血液透析对透析患者血小板细胞内游离钙及淋巴细胞膜表面β肾上腺素能受体密度的影响。１对象和方法１．１研究对象２５例尿毒症接受维持性血液透析的患者（男１４例，女１１例），年龄３５～６５（平均５２±３）岁。按有无慢性充血性心力衰竭分为心衰组（...     

去甲肾上腺素诱导心肌细胞肥大的机制

目的 :探讨去甲肾上腺素 (NE)诱导产生心肌细胞肥大的机制。方法 :采用测定心肌细胞直径及3 H 亮氨酸 (3 H leu)掺入率的方法 ,观察NE、哌唑嗪 (PRAZ)及普萘洛尔 (Pro)对SpragueWawley大鼠培养心肌细胞肥大的影响。结果 :NE可以促进心肌细胞直径增大及3 H leu掺入率的增加 (均P <0 .0 1)。PRAZ及Pro均可阻断NE的上述作用 ,以Pro的阻断作用最为显著。结论 :NE可促进心肌细胞肥大 ,而这种作用是通过PRAZ和Pro介导的 ,Pro起主要作用     

心肌缺血时心肌去甲肾上腺素的释放

去甲肾上腺素(NE)在心肌缺血病理过程中起重要作用,本文综述了心肌缺血的不同时期心肌NE释放规律及药物、心肌代谢产物对其释放的影响。     

急性心肌冬眠时心脏去甲肾上腺素的释放

目的：探讨急性心肌冬眠时心脏去甲肾上腺素的释放情况。方法：健康雄性SD大鼠36只,被随机分成对照组、冬眠组、冬眠-酪胺组、复灌组、复灌＋酪胺组和复灌＋去甲丙咪嗪＋酪胺组,每组6只。建立离体鼠心脏急性冬眠模型。用高效液相色谱法测定急性心肌冬眠时心脏去甲肾上腺素的自发性和电场刺激引起的释放．并评价去甲丙眯嗪和酪胺对去甲肾上腺素释放的影响及酪胺对心率的影响。结果：在冬眠组,缺血1min、120min和加入去甲丙咪嗪后冠脉流出液中去甲肾上腺素的含量分别为（1．9±0．5）．（2．0±0．4）和（1．9±0．4）pmol／g·min,三者之间差异没有显著性（P〉0．05）;电场刺激引起的心脏去甲肾上腺素的溢出在冬眠组为（3．2±1．3）pmol／g·min,对照组为（76．9±27．7）pmol／g·min,复灌组为（80．3±23．9）pmol／g·min,经方差分析。对照组和复灌组之间差异没有显著性（P〉0．05）。冬眠组较对照组以及复灌组显著减少（P〈0．01）;在冬眠-酪胺组和复灌＋酪胺组,酪胺均可引起心率和去甲肾上腺素溢出的明显增加（P〈0．05）,而在去甲丙眯嗪存在的情况下,这种增加变得不明显（P〉0．05）。结论：离体鼠心脏急性冬眠时,不伴有心脏去甲肾上腺素自发性释放的明显增加。而酪胺可引起心率和去甲肾上腺素释放的明显增加．提示心脏交感神经末梢的能量并没有被耗竭;电场刺激引起的心脏去甲肾上腺素释放明显减少。复灌后这种释放恢复至对照组水平．提示在急性心肌冬眠过程中,心脏的交感神经功能可能也经历了一个类似冬眠即神经冬眠的过程。     

去甲肾上腺素性心肌损伤心肌细胞线粒体琥珀酸脱氨酶的…

超生理剂量去甲肾上腺素造成兔心肌损伤模型，应用电镜细胞化学方法观察心肌细胞线粒体琥珀酸脱氢酶活性改变，应用去甲肾上腺素后线粒体琥珀酸脱氢酶活性均有显著下降，其中细胞超微结构及膜通透性均无明显下降，提示能量代谢障碍可能为去甲肾上腺素性心肌损伤的重要初始环节。     

原发性高血压病人尿去甲肾上腺素及肾上腺素的含量

对原发性高血压６０例，正常对照３１例的尿去甲肾上腺素及肾上腺素含量进行测定，以观察交感神经活性对的影响。ＥＨ组２４ｈ、日间、夜间ＵＮＥ含量显著高于正常组，而ＥＨ组ＵＥ含量与正常组比较则无显著差异。正常组ＵＮＥ含量日间显著高于夜间，ＥＨ组ＵＮＥ含量则无此昼夜规律性。以正常组ＵＮＥ均值加２ｓ作为正常高限，ＥＨ患者２４ｈ及夜间ＵＮＥ含量高于正常高限者分别占１９例及１２例，反映了部分ＥＨ患者交感神经活性可     

PAMP增强肾上腺素和去甲肾上腺素升血糖的作用

我们在研究肾上腺髓质素前体Ｎ端２０肽（ＰＡＭＰ）时，发现应用ＰＡＭＰ剂量在３０．０ｎｍｏｌ／ｋｇ时可引起大鼠心律失常发生率高达６４．７％。在５ｎｍｏｌ／ｋｇ时可明显增强肾上腺素（Ｅ）和去甲肾上腺素（ＮＥ）的致心律失常作用（未发表资料），而Ｅ也是升高血...     

粉防己碱对缺氧和复氧损伤心室肌细胞内Ca2+超载的作用

目的 :研究粉防己碱 (Tet)对培养大鼠心室肌细胞缺氧和复氧损伤时细胞内 Ca2 超载的作用。方法 :采用荧光探针 Fura- 2 / AM结合计算机图像处理技术测定单个心室肌细胞内 Ca2 浓度。结果 :对照组心室肌细胞在缺氧和复氧过程中出现 2次细胞内 Ca2 浓度明显上升 ,维拉帕米 (Ver)处理组 (10μmol/ L )心室肌细胞出现 2次细胞内 Ca2 浓度轻度上升 ;Tet处理组 (30 0μmol/ L )心室肌细胞未出现细胞内 Ca2 浓度上升。两处理组分别与对照组比较均有极显著性差异 (P<0 .0 1) ,两处理组间比较亦有显著性差异 (P<0 .0 5 )。结论 :Tet对缺氧和复氧损伤心室肌细胞内 Ca2 超载有较强的阻抑作用     

蛋白激酶C和Ca2+在心肌细胞预处理中的作用

目的：探讨心肌细胞缺氧预处理、蛋白激酶C（PKC）和细胞内钙离子在心肌细胞预处理中的作用。方法：在培养乳鼠心肌细胞缺氧预处理的模型上，观察缺氧预处理以及PKC抑制剂Chelerythrine和钙离子螯合剂BAPTA／AM对缺氧预处理的影响。结果：缺氧预处理可以减少缺氧／复氧对心肌细胞的损伤。PKC抑制剂Chelerythrine和钙离子螯合剂BAPTA／AM可以抑制缺氧预处理的心肌保护作用。结论：PKC和钙离子介导心肌细胞的缺氧预处理。     

辛伐他丁对大鼠肝贮脂细胞增殖周期和胞内钙浓度的影响

目的：观察辛伐他丁对大鼠肝贮脂细胞增歼击吉期以及胞内Ca^2 浓度的影响。方法：采用酶灌流法分离大鼠肝贮脂细胞，20％血清和10ng/mL PDGF诱导培养肝贮脂细胞，应用流式细胞仪检测肝贮脂细胞增殖周期，Fura/AM荧光法测定胞内Ca^2 浓度。结果：1－20μmol/L辛伐他丁可阻止血清和PDGF诱导大鼠肝贮脂细胞由G1期进入S期，降低肝贮脂细胞S期比、PI值和DNA含量，与对照组比较有显著性差异（P＜0．05）。同时，1－20μmoL/L辛伐他丁可明显降低血清和PDGF诱导培养的肝贮脂细胞胞内Ca^2 浓度，不呈剂量依赖性，与对照组比较有显著性差异（P＜0．05）。同时加入10mmoL/L甲羟戊酸可逆转辛伐他丁对大鼠肝贮脂细胞增殖周期以及胞内Ca^2 浓度的影响。结论：辛伐他丁可抑制大鼠肝贮脂细胞增殖生长，并降低肝贮脂细胞胞内Ca^2 浓度，其机制与辛伐他丁掏甲羟戊酸途径有关。     

High glucose level inhibits capacitative Ca2 + influx in cultured rat mesangial cells by a protein kinase C-dependent mechanism

Summary In cultured mesangial cells (MC), capacitative Ca^{2 +} influx via store-operated channels (SOC) is potentiated by agents that release Ca^{2 +} from intracellular stores, and inhibited by protein kinase C (PKC). Cells grown under high glucose conditions, as a model of the diabetic microenvironment, display reduced Ca^{2 +} signalling in response to vasoconstrictors, probably due to downregulation by elevated PKC activity. Since SOC might be relevant to this phenomenon, we assessed Ca^{2 +} influx by microfluorometry of fura-2-loaded rat MC cultured for 5 days in normal (5.5 mmol/l, NG) or high glucose (30 mmol/l, HG). The addition of 1–10 mmol/l Ca^{2 +} to NG cells equilibrated in Ca^{2 +} -free media induced an immediate Ca^{2 +} influx with a free cytosolic Ca^{2 +} ([Ca^{2 +} ]_i) plateau of 155 ± 50 and 318 ± 114 nmol/l, respectively. Basal influx was reduced to 88 ± 8 and 145 ± 17 nmol/l [Ca^{2 +} ]i (1–10 mmol/l Ca^{2 +} , p < 0.01) by 30 mmol/l d-glucose. This effect of HG was confirmed by Mn^{2 +} quenching of fura-2, indicating reduced entry of divalent cations via the capacitative pathway. Equimolar l-glucose had no effect on Ca^{2 +} influx, consistent with a non-osmotic mechanism. Arginine vasopressin (10 μmol/l) elicited weaker release of stored Ca^{2 +} and subsequent influx in HG cells (191 ± 33 vs 153 ± 24 nmol/l, 400 ± 76 vs 260 ± 33 nmol/l, 1–10 mmol/l Ca^{2 +} , NG/HG, p < 0.05). To examine the involvement of PKC in the effect of HG on capacitative Ca^{2 +} influx, the enzyme was activated or downregulated by treatment with 0.1 μmol/l phorbol myristate acetate (PMA) for 3 min or 24 h, respectively. PMA acutely inhibited Ca^{2 +} influx in NG cells, while PKC downregulation restored it in HG cells. Similarly, the PKC inhibitors staurosporin or H-7 normalized SOC activity in HG cells. In summary, impairment of Ca^{2 +} influx via SOC by HG is one mechanism of the reduced MC [Ca^{2 +} ]_i responsiveness to vasoconstrictors. This event is mediated by PKC and may contribute to the glomerular haemodynamic changes in the initial stages of diabetes mellitus. [Diabetologia (1997) 40: 521–527] Received: 25 November 1996 and in revised form: 30 January 1997     

Hepatic stellate cells express Ca2+ pump-ATPase and Ca2+-Mg2+-ATPase in plasma membrane of caveolae

Intracytoplasmic free calcium ions (Ca²⁺) are maintained at a very low concentration in mammalian tissue by the extrusion of Ca²⁺ across a steep extracellular Ca²⁺ gradient, mainly through the activity of plasma membrane Ca²⁺ pump-ATPase. The present study aimed to identify, by electron cytochemical and electron immunogold methods, the ultrastructural localizations of two types of plasma membrane Ca²⁺-ATPase; Ca²⁺-Mg²⁺-ATPase and Ca²⁺ pump-ATPase, in hepatic stellate cells. Liver tissues and isolated hepatic stellate cells (HSCs) were studied. The ultrastructural localization of Ca²⁺-Mg²⁺-ATPase activity was examined by the electron cytochemical method of Ando. The localization of Ca²⁺ pump-ATPase was identified by immunofluorescence. The ultrastructural localization of Ca²⁺ pump-ATPase was identified by the electron immunogold method. The cytochemical reaction products of Ca²⁺-Mg²⁺-ATPase activity were localized on the outer (cavity) side of the plasma membrane of caveolae. Immunofluorescence of Ca²⁺ pump-ATPase was seen as small dots along the cell edge in HSCs. Immunogold particles indicating the presence of Ca²⁺ pump-ATPase were identified on the inner (cytoplasmic) side of the plasma membrane of caveolae. We localized Ca²⁺ pump-ATPase on the inner side of the plasma membrane caveolae and Ca²⁺-Mg²⁺-ATPase on the outer leaflet of the caveolar plasma membrane in stellate cells, suggesting that Ca²⁺ pump-ATPase may play a key role in the Ca²⁺ reflux. Received: March 7, 2000 / Accepted: July 7, 2000     

Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes

In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca(2+) handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca(2+) transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca(2+) transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca(2+) concentration ([Ca(2+)](o)), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca(2+) level and peak intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca(2+)](i) transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca(2+)](i) transient was not normalized by increasing [Ca(2+)](o) to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca(2+) release. Blockade of sarcoplasmic reticulum (SR) Ca(2+)-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca(2+)](o), which was slowed in IL-2-treated myocytes when [Ca(2+)](o) was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca(2+)](o). The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na(+)-Ca(2+) exchange activity, but not to any change in L-type Ca(2+) channels.     

冠状动脉平滑肌细胞大电导钙离子激活钾通道电流的特点

Objective To investigate characteristics of large conductance Ca2+ -activated K+ currents ( BK currents) in normal rat coronary smooth muscle cells. Methods Coronary smooth muscle cells were isolated by enzyme digestion. Potassium channels in coronary smooth muscle cells were identified by applications of different potassium blockers. BK currents were recorded by patch clamp in whole ce11 and single channel configuration,respectively. BK currents amplitude and conductance were calculated. Voltage-sensitive and calciumsensitive characteristics of BK currents and changes with IBTX,a specific blocker,were observed. Results BK currents in normal smooth muscle cells accounted for 65% ± 4% of total potassium currents( n = 12), BK current conductance was (258 ± 42) pS ( n = 6), and current densities were ( 275 ± 40 ) pA/pF at voltage 150 mV ( n = 8). Open probabilities ( NP0 ) of BK channels at calcium 1 μmol/L in external solution and test potentials at 0,20,40,60,80,100,120,140 and 160 mV were 0,0. 0002,0. 0016 ± 0. 0005,0. 0283 ± 0. 0081,0. 05694 ±0. 0102,0. 3533 ± 0. 0514,1. 4922 ± 0. 1578,2. 5975 ± 0. 3632, and 4. 6041 ± 0. 7834, respectively (P＜0.05,n =5). NP0 of BK channels at test potential 60 mV,and calcium in external solution at 0,0. 001,0. 01,0. 1,1,10,50 and 100 μmol/L were 0,0.0001,0.0031 ± 0.0008,0.0042 ± 0.0090,0.0808 ± 0.0105,0.7591 ±0. 1274,2.7242 ±0.4612,and 3.2366 ±0.5728,respectively(P ＜0.05,n =6). Conclusion BK channels are widely distributed in normal coronary smooth muscle cells, have voltage-sensitive and calcium-sensitive characteristics, and play an important role in regulation of coronary vascular tension.     

Agonist-specific Ca2+ signaling systems, composed of multiple intracellular Ca2+ stores, regulate gonadotropin secretion

Ca²⁺ signals regulate many cellular functions, including hormone secretion. Agonist-specific Ca²⁺ signaling may arise from the differential mobilization of multiple Ca²⁺ stores. Although they act through the same receptor subtype, two gonadotropin-releasing hormones (sGnRH and cGnRH-II) generate quantifiably different Ca²⁺ signals in goldfish gonadotropes, suggesting that their Ca²⁺-dependent signaling cascades may differ. We combined electrophysiology, Ca²⁺ imaging, and radioimmunoassay detection of gonadotropin (GTH-II) secretion to determine the role of intracellular Ca²⁺ stores in GnRH-stimulated exocytosis. Our findings suggest that voltage-gated Ca²⁺ channels do not mediate acute GnRH-signaling. Instead, both sGnRH- and cGnRH-II-stimulated GTH-II releases are dependent on Ca²⁺ mobilized from TMB–8/CPA-sensitive compartments. However, sGnRH, but not cGnRH-II, utilizes intracellular stores sensitive to caffeine and xestospongin C. We also identified a homeostatic mechanism where reduced extracellular Ca²⁺ availability increase GTH-II release by mobilizing Ca²⁺ stores. Our results are the first to suggest that several classes of intracellular Ca²⁺ stores differentially participate in agonist signaling and homeostasis in gonadotropes.     

冠状动脉平滑肌细胞大电导钙离子激活钾通道电流的特点

目的探讨正常大鼠冠状动脉平滑肌细胞大电导钙离子激活钾通道（BK通道）电流的特点,为研究疾病状况下冠状动脉平滑肌细胞BK通道电流异常变化提供正常对照。方法酶消化法分离大鼠冠状动脉平滑肌细胞;采用不同阻滞剂,对冠状动脉血管平滑肌细胞上钾通道进行鉴定;采用全细胞和单通道膜片钳实验技术分别记录冠状动脉平滑肌细胞BK通道电流,计算开放幅度和电导,观察BK通道电压敏感性和钙敏感性及加入特异性BK通道阻滞剂IBTX后BK通道电流的变化。结果正常冠状动脉平滑肌细胞BK通道电流约占总钾离子流65％±4％（t／,=12）,BK通道电导为（258±42）pS（n=6）,在刺激电位150mV时,电流密度为（275±40）pA／pF（n=8）;在电极外液钙离子浓度为1μmol／L,刺激电位为0、20、40、60、80、100、120、140和160mV条件下,BK通道开放概率（NP0）分别为0、0．0002、0．0016±0．0005、0．0283±0．0081、0．05694±0．0102、0．3533±0．0514、1．4922±0．1578、2．5975±0．3632和4．6041±0．7834（P〈0．05,n=5）;在刺激电位60mV,电极外液钙离子浓度为0、0．001、0．01、0．1、1、10、50和100μmol／L条件下,BK通道NP。分别为0、0．0001、0．0031±0．0008、0．0042±0．0090、0．0808±0．0105、0．7591±0．1274、2．7242±0．4612和3．2366±0．5728（P〈0．05,n=6）。结论BK通道广泛分布于冠状动脉平滑肌细胞上,具有电压敏感性和钙敏感性,对冠状动脉血管张力调节起重要作用。