Dofetilide对成年豚鼠心室肌细胞钠钙交换的影响

目的　研究dofetilide对豚鼠心室肌细胞Na+ /Ca2 + 交换电流的影响。方法　酶法分离成年豚鼠心室肌细胞 ,全细胞膜片钳方式、斜坡电压刺激程序 (从钳制电位 - 4 0mV去极化至 +6 0mV ,然后以 90mV/s的速率超极化至 - 12 0mV)记录Na+ /Ca2 + 交换电流 (INa/Ca)及dofetilide 0 0 3～ 1 0μmol·L-1对该电流的影响。结果　dofetilide 0 0 3～ 1 0μmol·L-1浓度依赖性地增强Na+ /Ca2 + 交换外向及内向电流 ,对外向电流的EC50 (5 0 %最大效应浓度 )为 0 178μmol·L-1(95 %可信限为 0 0 4 0～ 0 787μmol·L-1) ,对内向电流的EC50 为 0 178μmol·L-1(95 %可信限为 0 0 38～ 0 84 2μmol·L-1)。结论　dofetilide对豚鼠心室肌细胞Na+ /Ca2 +交换外向及内向电流均有浓度依赖性的明显增强作用。     

酪氨酸蛋白激酶在不同α_1肾上腺素受体亚型Ca~(2+)调控中的作用

目的　了解酪氨酸蛋白激酶信号途径在不同α1肾上腺素受体亚型Ca2 +调控中的作用。方法　用Fura 2荧光探针双波长测定细胞胞浆游Ca2 +浓度 ([Ca2 +]i)的方法 ,在分别转染了α1A、α1B和α1D肾上腺素受体cDNA的HEK2 93细胞 ,观察酪氨酸蛋白激酶抑制剂Genistein和磷脂酶C抑制剂U7312 2 对激动不同α1肾上腺素受体亚型引起的 [Ca2 +]i 变化的影响。结果　预先用U7312 2 (0 1,10 ,5 0 μmol·L-1)与细胞共同孵育 10min ;用Genistein(10 ,10 0 ,2 0 0 μmol·L-1)与细胞共同孵育 1h。在分别转染了α1A、α1B和α1DcDNA的HEK2 93细胞 ,U73 12 2 和Genistein均能浓度依赖性地抑制肾上腺 (10 μmol·L-1)引起的双相 [Ca2 +]i 的升高。在上述细胞 ,U7312 2 (5 0 μmol·L-1)能完全抑制肾上腺素引起的[Ca2 +]i 升高 ;而用最大有效浓度 10 0 μmol·L-1的Genistein只能部分抑制肾上腺素升高 [Ca2 +]i 的作用。结论　在HEK 2 93细胞 ,不同α1肾上腺素受体亚型 (α1A α1B和α1D)激动均能部分通过酪氨酸蛋白激酶信号途径引起Ca2 +释放和Ca2 +内流。α1肾上腺素受体可能通过G蛋白和酪氨酸蛋白激酶两种途径激活磷脂酶C     

激动α_(1B)-肾上腺素受体对DDT1 MF-2细胞生长的刺激作用及其途径

目的　研究激动α1B 肾上腺素受体 (α1B AR)对DDT1MF 2细胞生长的影响及其机制。方法　用3H-胸腺嘧啶参入法测定细胞的DNA合成速率 ;用流式细胞计测定细胞周期。结果　去甲肾上腺素 (NE ,0 1～ 1μmol·L-1)可刺激DDT1MF 2细胞DNA的合成。磷脂酶C抑制剂 (U7312 2 ,10 μmol·L-1)、Ca2 +/ATP酶抑制剂 (CPA ,10 μmol·L-1)、胞内Ca2 +络合剂 (BAPTA/AM ,10 μmol·L-1)、PKC抑制剂(RO 31 82 2 0 ,0 1μmol·L-1或calphostinC ,0 1μmol·L-1)、酪氨酸激酶抑制剂 (tyrphostinA2 5 ,10 μmol·L-1或genis tein ,10 μmol·L-1)、MEK1/ 2抑制剂 (PD 980 5 9,10 μmol·L-1)均可阻断NE刺激细胞DNA合成的作用。结论　激动α1B AR可刺激DDT1MF 2细胞增殖 ,其信号转导途径可能与PLC激活、Ca2 +释放、PKC、TK和ERKs的激活有关     

四肽FMRFa对大鼠心室肌Na^＋／Ca^2＋交换的抑制

目的　研究四肽FMRFa对大鼠单个心室肌细胞Na /Ca2 交换的作用。方法　用膜片钳全细胞记录法测定成年大鼠心室肌细胞Na /Ca2 交换电流 (INa /Ca2 )和其他离子通道电流。结果　FMRFa对大鼠心室肌细胞INa /Ca2 呈浓度依赖性抑制 ,10 0 μmol·L-1浓度时抑制内向和外向INa /Ca2 密度分别达 6 0 1%和 5 6 5 % ,对内向电流及外向电流的IC50 分别为 2 0 μmol·L-1和 34μmol·L-1。FMRFa 5 μmol·L-1抑制INa /Ca2 内向和外向电流密度分别为 38 7%和 34 9% ,但FMRFa 5 μmol·L-1及 2 0 μmol·L-1对L型钙电流、钠电流、瞬时外向电流和内向整流钾电流均无显著抑制作用。结论　FMRFa对大鼠心室肌细胞是一个特异性Na /Ca2 交换抑制剂。     

染料木素对离体豚鼠乳头肌生理特性的影响

目的观察比较染料木素(genistein,Gen)和17β-雌二醇(17β-estradiol,Est)对豚鼠乳头肌生理特性影响,研究Gen对豚鼠离体心肌的兴奋作用与肌质网Ca2+释放和摄取的关系。方法将乳头肌置于装有K-H液的灌流肌槽中,加入药物观察其生理特性及收缩活动的变化。结果Gen及17β-雌二醇浓度为1和10μmol·L-1均不影响肾上腺素诱发的心肌自律性,二者在50μmol·L-1时均能抑制自律性;Gen浓度为50μmol·L-1能降低心肌兴奋阈强度,Gen(1和10μmol·L-1)及17β-雌二醇(1～50μmol·L-1)不影响兴奋性阈强度;Gen(1～50μmol·L-1)不影响心肌功能不应期(FRP),17β-♂二醇(1～50μmol·L-1)延长心肌FRP;同时发现1～50μmol·L-1的17β-雌二醇抑制心肌的收缩活动,但同浓度的Gen可增强心肌的收缩活动。利罗丁(ryanodine)受体阻断剂钌红(10μmol·L-1)和利罗丁(1nmol·L-1)预处理可部分阻断Gen(50μmol·L-1)对心肌收缩的增强效应,利罗丁(20μmol·L-1)使Gen正性肌力作用完全阻断。肌质网钙泵阻断剂thapsigargin(1μmol·L-1)预处理也可部分抑制Gen(50μmol·L-1)对心肌收缩的兴奋作用。但特异性雌激素受体(ER)阻断剂ICI182,780(10μmol·L-1)和Na+-Ca2+逆交换抑制剂Kb-R7943(1μmol·L-1)预处理不影响Gen(50μmol·L-1)的正性肌力作用。结论Gen和17β-雌二醇均能降低心肌兴奋性和自律性,但Gen增强其收缩活动,而17β-雌二醇作用相反;Gen正性肌力作用与心肌细胞膜上的ER和Na+-Ca2+逆交换无关,可能与肌质网内Ca2+的释放和摄取有直接的关系。     

Ca~(2+)运动对α_1-肾上腺素受体引起内源性ClC-3氯通道表达的作用

目的　研究Ca2 +运动对α1 肾上腺素受体引起ClC 3氯通道表达的作用。方法　在A10细胞上 ,用RT PCR和Westernblot检测ClC 3mRNA和蛋白质表达情况。结果　苯肾上腺素 ( 10 μmol·L-1)和thapsigargin( 0 1μmol·L-1)可促进ClC 3mRNA和蛋白质的表达 ;SK&F963 65 ( 10 μmol·L-1)和genistein( 10 μmol·L-1)可抑制苯肾上腺素引起的ClC 3的表达 ,nifedipine( 10 μmol·L-1)无此作用。结论　在A10细胞上 ,通过钙池操纵性Ca2 +通道 (SOCC)的Ca2 +内流参与了α1 肾上腺素受体引起的内源性ClC 3氯通道的表达 ,而通过电压依赖性Ca2 +通道 (VDCC)的Ca2 +内流可能与此无关。蛋白酪氨酸激酶参与了ClC 3氯通道的表达     

槲皮素单硫酸酯钠对 HL-60细胞生长的影响(英文)

通过观察槲皮素单硫酸酯钠 (SQMS)对 HL-60细胞毒作用 ,细胞周期变化 ,胞内 Ca2 +浓度([Ca2 +]i)变化及蛋白激酶 CK2活性的变化研究SQMS对 HL- 60细胞生长的影响 .发现 SQMS(2 0- 1 2 0μmol· L-1)可浓度依赖性抑制 HL- 60细胞的生长 ,阻断 HL- 60细胞于 G0 /G1期 ;SQMS(1 0 0μmol· L-1)可使 [Ca2 +]i 由 (1 0 5± 9) nmol·L-1上升到 (2 0 1± 1 3) nmol· L-1;低浓度 SQMS(0 .55-8.8μmol· L-1)可显著抑制从 HL- 60细胞中纯化的蛋白激酶 CK2的活性 .结果提示 ,SQMS可抑制HL- 60细胞生长 ,其机理可能与抑制 HL- 60细胞中蛋白激酶 CK2的活性 ,提高细胞 [Ca2 +]i 及促进细胞分化有关 .     

垂体腺苷酸环化酶激活肽减轻谷氨酸引起的大鼠海马神经元细胞内钙离子浓度升高的可能机理

目的　探讨垂体腺苷酸环化酶激活肽 38(PACAP 38)稳定海马神经元细胞内钙离子浓度([Ca2 + ]i)作用的可能机理。方法　取新生SD大鼠海马 ,用B2 7无血清培养基培养神经元 ;经Fura 2 /AM标记后 ,共聚焦显微镜下测定 [Ca2 + ]i。结果PACAP 38(10pmol·L- 1)能抑制谷氨酸 (5 0 0 μmol·L- 1)所致海马神经元 [Ca2 + ]i 升高 ,而Rp型硫化环腺苷酸 (2 0 μmol·L- 1)或氯化白屈菜赤碱 (0 .1μmol·L- 1)能阻断PACAP 38的抑制作用。二丁基环腺苷酸 (0 .1～ 10 0 μmol·L- 1)和豆寇酰佛波醇乙酯(0 .0 1～ 10 μmol·L- 1)也能抑制谷氨酸引起的海马神经元 [Ca2 + ]i 升高。结论　PACAP 38减轻谷氨酸引起的海马神经元 [Ca2 + ]i 升高可能与激活细胞内蛋白激酶A和蛋白激酶C信号转导系统有关     

抗心肌Na~+/Ca~(2+)交换体α-1_(138-177)抗体对心力衰竭大鼠心肌Na~+/Ca~(2+)交换电流的抑制作用

目的观察抗心肌Na+/Ca2+交换体α-1(138-177)抗体对心力衰竭大鼠心肌Na+/Ca2+交换电流的影响。方法通过腹主动脉结扎建立心力衰竭模型,利用人工合成的多肽免疫兔制备抗α-1抗体,应用酶解法分离心肌细胞,利用全细胞膜片钳技术观察抗α-1抗体对心力衰竭大鼠心肌Na+/Ca2+交换电流的作用。结果 10μmol/L的抗α-1抗体使内向和外向的Na+/Ca2+交换电流分别从给药前的(9.0±2.7)、(13.7±3.6)pA/pF降至(4.5±1.7)、(6.5±2.3)pA/pF(P<0.05)。结论抗α-1(138-177)抗体对心力衰竭大鼠心肌细胞Na+/Ca2+交换电流具有抑制效应。     

抗心律失常药E-4031通过蛋白激酶C途径影响豚 鼠心室肌细胞Na+/Ca2+交换 (英文)

应用全细胞电压钳技术的斜坡脉冲程序 ,测定离体豚鼠心肌细胞准稳态电流 -电压关系曲线 ,研究E- 40 31增强 Na /Ca2 交换电流的机理 .结果表明蛋白激酶 C激动剂十四酰佛波乙酯 ( TPA) 5,1 0和1 5nmol· L-1使膜电位 50 m V时的 Ni2 敏感电流分别增加 ( 1 1 6± 43) % ,( 2 2 5± 63) %和 ( 2 89±69) % .使膜电位 - 1 0 0 m V时的 Ni2 敏感电流分别增加 ( 2 9± 1 7) % ,( 1 0 4± 2 1 ) %和 ( 1 40± 2 9) % .蛋白激酶 C拮抗剂他莫昔芬 2 0 μmol· L-1可完全阻断 E- 40 31和 TPA对该电流的刺激作用 .结果提示 ,E- 40 31通过蛋白激酶 C途径激动 Na /Ca2 交换 .     

AMP579与腺苷对大鼠和豚鼠心室肌钾离子或钠离子通道作用的比较

目的研究AMP579和腺苷对钾离子与钠离子通道的影响及其作用机制，比较它们对负性变力及抗心律失常作用的离子机制。方法采用膜片钳全细胞记录模式记录大鼠和豚鼠心室肌细胞离子通道电流。结果腺苷对大鼠心室肌瞬时外向钾电流(I_{to)的激动作用强于AMP579，腺苷和AMP579的EC50值分别为2.33与8.32 μmol·L^-1 (P<0.05)；两者激动Ito的作用均可被腺苷A1受体阻滞剂PD116948阻断，表明其作用机制均是通过腺苷A1受体介导的。腺苷对豚鼠心室肌延迟整流钾电流(IK)的抑制作用强于AMP579，腺苷和AMP579的IC50值分别为1.21与2.31 μmol·L^-1 (P<0.05)；AMP579对内向整流钾电流(IK1)的抑制作用强于腺苷，AMP579和腺苷的IC50值分别为4.15与20.7 μmol·L^-1 (P<0.01)。AMP579和腺苷对大鼠心室肌钠电流(INa)的抑制作用相似，其IC50值分别为9.46与6.23 μmol·L^-1。结论腺苷对大鼠心室肌Ito的激动作用强于AMP579，两者对Ito的作用机制均是通过腺苷A1受体介导的。AMP579对IK1的抑制作用强于腺苷，而腺苷对IK的抑制作用强于AMP579，两者对INa的抑制作用相似，这些离子机制与两者发挥负性变力与抗心律失常作用有关系。}     

Effects of AMP579 and adenosine on L-type Ca^2＋ current in isolated rat ventricular myocytes

Aim: To compare the effects of AMP579 and adenosine on L-type Ca^2 current (ICa-L) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on ICa-L.Methods: ICa-L was recorded by patch-clamp technique in whole-cell configuration. Results: Adenosine (10nmol/L to 50μmol/L) showed no effect on basal ICa-L, but it inhibited the ICa-L induced by isoproterenol 10nmol/L in a concentration-dependent manner with the IC50 of 13.06μmol/L. Similar to adenosine,AMP579 also showed an inhibitory effect on the ICa-L induced by isoproterenol.AMP579 and adenosine (both in 10μmol/L) suppressed isoproterenol-induced ICa-L by 11.1% and 5.2%, respectively. In addition, AMP579 had a direct inhibitory effect on basal ICa-L in a concentration-dependent manner with IC50(1. 17μmol/L). PD116948 (30μmol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal ICa-L. However, GF109203X (0.4μmol/L), a special protein kinase C (PKC) blocker, could abolish the inhibitory effect of AMP579 on basal ICa-L. So the inhibitory effect of AMP579 on basal ICa-L was induced through activating PKC, but not linked to adenosine A1 receptor. Conclusion:AMP579 shows a stronger inhibitory effect than adenosine on the ICa-L induced by isoproterenol. AMP579 also has a strong inhibitory effect on basal ICa-L in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal ICa-L at downstream-mechanism.     

Inhibitory effects of AMP 579, a novel cardioprotective adenosine A1/A2A receptor agonist, on native I Kr and cloned HERG current

We investigated the effects of 1S-[1a,2b,3b,4a(S*)]-4-[7-[[1-[(3-chloro-2-thienyl)methylpropyl]propyl-amino]-3H-imidazo[4,5-b] pyridyl-3-yl]-N-ethyl-2,3-dihydroxycyclopentane carboxamide (AMP 579), a novel cardioprotective adenosine A₁/A_2A receptor agonist, on the rapid and slow components of the delayed rectifier K⁺ current (I_Kr and I_Ks) in guinea-pig ventricular myocytes and on the human ether-a-go-go-related gene (HERG) channel expressed in human embryonic kidney (HEK 293) cells. Whole-cell current and membrane potential were recorded using patch-clamp techniques. In guinea-pig ventricular myocytes, AMP 579 inhibited I_Kr in a concentration-dependent manner with IC₅₀ value of 15.2 M, when I_Kr was blocked by chromanol 293B. On the contrary, AMP 579 (10 M) did not affect I_Ks in the presence of the I_Kr blocker E-4031. The former effect of AMP 579 was unaffected by either the selective adenosine A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or the non-selective adenosine A₁/A₂ receptor antagonist 8-sulphophenyltheophylline. Moreover, AMP 579-induced inhibition of I_Kr was not voltage- and frequency-dependent. In HEK 293 cells expressing HERG channels, AMP 579 (10 M) significantly blocked the HERG current at +10 mV by 34.9±7.0% (n=4, p<0.05), and the degree of inhibition was comparable with that observed in guinea-pig ventricular myocytes (36.8±6.0%, n=4). AMP 579 (10 M) significantly inhibited the L-type Ca²⁺ current (I_Ca) by 41.0±6.8% (n=5, p<0.05), which was unaffected by 8-sulphophenyl-theophylline. Consequently, despite its inhibitory actions on I_Kr or HERG current, the drug significantly shortened the action potential duration measured at 90% repolarization from 275.6±19.4 to 208.3±18.6 ms (n=4, p<0.05). Thus, AMP 579 inhibits both native I_Kr and cloned HERG channels with additional inhibitory effect of I_Ca, and such inhibitory effects may at least partially underlie the observed antifibrillatory action of the drug during myocardial ischemia/reperfusion.     

A novel adenosine analog, AMP579, inhibits neutrophil activation, adherence and neutrophil-mediated injury to coronary vascular endothelium

We hypothesized that 1S-[1a,2b,3b, 4a(S*)]-4-[7-[[1-[(3-chloro-2-thienyl)methylpropyl]propyl-amino]-3H-i midazo[4,5-b] pyridyl-3-yl]-N-ethyl-2,3-dihydroxycyclopentane carboxamide (AMP579), a new adenosine analog, inhibits superoxide anion (O(2)(-)) generation and degranulation from canine neutrophils, neutrophil adherence and neutrophil-induced dysfunction to canine coronary artery endothelium by adenosine receptor-mediated mechanisms. AMP579 inhibited O(2)(-) generation (nM/20x10(6) neutrophils) from platelet activating factor (PAF)-activated neutrophil in concentration-dependent manner (4.1+/-0.8 at 10 microM vs. 16.7+/-2.1 in PAF group, P<0.05). This inhibitory effect was blocked by the adenosine A(2A) receptor-selective antagonist, 4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3, 5]triazin-5-ylamino]ethyl)phenol (ZM241385, 17.7+/-2.8, P<0.05), but not by either the adenosine A(1) receptor-selective antagonist, 8-Cyclopentyl-1.3-dipropylxanthine (DPCPX) or the adenosine A(3) receptor-selective antagonist, 9-Chloro-2-(2-furanyl)-5-[(phenylacetyl)amino][1,2,4]-triazolo[1, 5-c]quinazoline (MRS1220). AMP579 inhibited neutrophil degranulation dose-dependently by 38+/-2% at 10 microM (P<0.05). The inhibitory effect of AMP579 was not altered by either DPCPX or MRS1220, but was partially reversed by ZM241385 (69+/-8%, P<0.05 vs. AMP579 10 microM). A total of 10 microM AMP579 reduced neutrophil adherence to thrombin-stimulated endothelium (neutrophils/mm(2)) from 269+/-16 to 44+/-4 (P<0.05); this was reversed by ZM241385, but not by DPCPX or MRS1220. After coincubation of unstimulated neutrophil with thrombin-stimulated endothelium, concentration-relaxation responses to the endothelium receptor-dependent vasodilator, acetylcholine, were reduced (maximum 57+/-5% vs. 120+/-5% in controls, P<0.05). This endothelial dysfunction was attenuated by AMP579 (116+/-7%, P<0. 05). We conclude that AMP579 inhibits neutrophil activation and neutrophil-mediated coronary endothelial dysfunction, primarily by an adenosine A(2A) receptor mechanism.     

腺苷与AMP579对冠心病患者中性粒细胞表面CD11b/CD18表达的影响

目的:探讨不同剂量腺苷与AMP579对不同类型冠心病(CHD)患者中性粒细胞表面CD11b/CD18表达的影响。方法:选择经临床症状、心电图改变及心肌酶学确诊的CHD患者及正常健康者采血,患者血液分别给予不同剂量的腺苷与AMP579进行干预,免疫荧光标记后用流式细胞仪分别检测正常人及患者用药前后中性粒细胞CD11b/CD18的表达值。结果:CHD患者的中性粒细胞CD11b/CD18的表达较正常人明显升高(P<0.01);腺苷在10,30,100μmol能有效降低CHD患者的中性粒细胞CD11b/CD18的表达(P<0.05),但30,100μmol组之间差异无显著性(P>0.05);AMP579组中,患者中性粒细胞CD11b/CD18的表达均未见明显降低,各组较对照组差异均无统计学意义(P>0.05)。结论:CHD的发生与CD11b/CD18表达升高有关;腺苷可通过降低CD11b/CD18的表达而降低白细胞与内皮细胞之间的黏附性;而AMP579在1,10,30μmol尚不能降低CHD患者CD11b/CD18的表达。     

Class III anti-arrhythmia drug E-4031 potentiates Na+/Ca2+ exchange current in rat ventricular myocytes

AIM: To study the effects of E-4031 on the Na+/Ca2+ exchange currents (INa/Ca). METHODS: The quasi-steady state current-voltage relationship from the isolated rat ventricular myocytes was measured using whole-cell voltage-clamp techniques with a ramp pulse protocol. RESULTS: At potential of mV, E-4031 5, 10, and 20 mumol.L-1 increased Ni(2+)-sensitive current from (0.48 +/- 0.12), to (0.78 +/- 0.20), (0.96 +/- 0.16), and (1.15 +/- 0.13) pA/pF, respectively; tetradecanoylphorbol acetate (TPA) 50 nmol.L-1 increased Ni(2+)-sensitive current from (0.60 +/- 0.16) to (1.33 +/- 0.25) pA/pF. Tamoxifen 20 mumol.L-1 completely prevented the current changes induced by E-4031 and TPA. CONCLUSION: E-4031 stimulates the Na+/Ca2+ exchange via a protein kinase C-dependent pathway.     

KB-R7943对豚鼠心室肌细胞Na+-Ca2+交换电流的作用

目的　观察KB-R7943对豚鼠心室肌细胞Na⁺-Ca²⁺交换电流(I_Na-Ca)的内向电流成分和外向电流成分的影响。方法　采用缺血再灌时胞内Na⁺超载的细胞模型,在同时记录内向、外向电流的双向离子条件下,用膜片钳全细胞技术,记录I_Na-Ca的电流-电压关系曲线。结果　10^-6和10^-5mol·L^-1KB-R7943,在+50mV时,对I_Na-Ca的抑制率分别是29.4%和61.7%;在-80mV时抑制率分别是22.1%和56.9%。结论　KB-R7943对豚鼠心室肌细胞I_Na-Ca有抑制作用,但对外向成分和内向成分的抑制不具选择性。     

Cardiovascular pharmacology of the adenosine A1/A2-receptor agonist AMP 579: coronary hemodynamic and cardioprotective effects in the canine myocardium

The hemodynamic and cardioprotective properties of the novel adenosine A1/A2 receptor agonist AMP 579 (IS-[1a,2b,3b,4a(S*)]-4-[7-[[1-[(3-chloro-2-thienyl)methyl]propylamino]- 3H-imidazo[4,5-b]pyridin-3-yl]-N-ethyl-2,3-dihydroxy cyclopentanecarboxamide) were studied in two canine models designed to simulate (a) mild single-vessel coronary artery disease, and (b) myocardial ischemia/reperfusion injury. In the first model, a moderate stenosis was placed on the left circumflex coronary artery (LCCA), and the effects of AMP 579 on regional myocardial blood flow were assessed. AMP 579, 10 micrograms/kg/min, i.v., for 10 min, induced coronary dilation without causing endocardial steal. In the model of ischemia/reperfusion injury (60 min LCCA occlusion/5 h reperfusion), AMP 579, 10 micrograms/kg/min, i.v., administered for 15 min before ischemia significantly decreased myocardial infarct size. Control infarct size to area at risk (IS/AAR) equaled 34 +/- 3% (n = 9); IS/AAR for AMP 579-treated dogs equaled 16 +/- 4% (n = 9). Preconditioning (5 min LCCA occlusion + 10 min reperfusion) immediately before the 60-min LCCA occlusion also resulted in a marked decrease in IS/AAR: 9 +/- 3% (n = 6). The selective A1 agonist CPA reduced infarct size when administered at 3 micrograms/kg/min, i.v., for 15 min before LCCA occlusion: IS/AAR = 11 +/- 3% (n = 5). Pretreatment of animals with the adenosine-receptor antagonist 8-SPT, 10 mg/kg, i.v., attenuated the myocardial protective effects associated with preconditioning, CPA, and AMP 579, resulting in IS/AAR values of 28 +/- 7% (n = 7), 28 +/- 4% (n = 8), and 26 +/- 3% (n = 8), respectively. The ability of 8-SPT to block the cardioprotective effects suggests that these effects were mediated through an interaction with adenosine receptors. These experimental results indicate that AMP 579 is an effective coronary vasodilator, which also can protect the heart from ischemic injury. Thus AMP 579 has the potential to be useful in cardiovascular therapeutics.     

山楂水提取物对猪离体冠状动脉环的舒张作用研究

目的:研究山楂水提取物对猪离体冠状动脉环的舒张作用。方法:观察0.1、0.3、0.5mg·mL-1山楂水提取物对KC(l30mmol·L-1)诱发的猪离体冠状动脉环收缩的舒张作用。以Na+/Ca2+交换体阻滞剂KB-R7943(1×10-6mol·L-1)、电压依赖性钾通道(KV)阻滞剂四胺基吡啶(4-AP,1×10-3mol·L-1)、K+-ATP通道阻滞剂格列苯脲(Gli,1×10-5mol·L-1)、K+/Ca2+通道阻滞剂乙胺(TEA,1×10-2mol·L-1)、内向整流钾通道(KiR)阻滞剂氯化钡(BaCl2,1×10-3mol·L-1)预处理血管环,观察其对山楂水提取物舒血管作用的影响。结果:山楂水提取物对KCl预收缩的猪离体冠状动脉环产生浓度依赖性的舒张作用。用KB-R7943、4-AP、Gli预处理的血管环对山楂水提取物的舒张反应与未经处理时比较无显著性差异(P>0.05)。TEA和BaCl2预处理的血管环对山楂水提取物的舒张反应与未经处理时比较有显著性差异(P<0.01)。结论:山楂水提取物对KCl预收缩的猪离体冠状动脉环具有浓度依赖性的舒张作用,其舒张反应可能与K+/Ca2+通道和KiR通道有关,与Na+/Ca2+交换体、KV通道和K+-ATP通道无关。