多沙唑嗪及其手性对映体对离体兔血管α_1 受体的拮抗特性(英文)

目的　分析α1 肾上腺素受体阻断药多沙唑嗪手性对映体对兔胸主动脉和颈总动脉的选择性作用 ,以探讨作为良性前列腺增生症治疗药物的可能性。方法　测定去甲肾上腺素 (NE)诱发兔离体胸主动脉和颈总动脉收缩反应 ,并采用Schild作图法计算rac 多沙唑嗪、R 多沙唑嗪和S 多沙唑嗪的pA2 值。结果　在兔胸主动脉和颈总动脉 ,0 .0 3 ,0 .1和 0 .3μmol·L-1 的rac 多沙唑嗪、R 多沙唑嗪和S 多沙唑嗪均使NE诱发的血管收缩反应量效曲线平行右移 ,Emax不变 ;由Schild作图法计算得到的多沙唑嗪及其手性对映体的斜率值 ,经统计学分析符合竞争性拮抗。3种拮抗剂pA2 值的强度顺序为 :R 多沙唑嗪 >rac 多沙唑嗪 >S 多沙唑嗪。结论　与多沙唑嗪及其手性对映体对人前列腺组织作用的报道结果不同 ,S 多沙唑嗪对兔胸主动脉和颈总动脉α1 肾上腺素受体拮抗作用的选择性显著低于rac 多沙唑嗪和R 多沙唑嗪     

多塞平对离体兔基底动脉环和隐动脉环的作用

目的：观察多塞平（ｄｏｘｅｐｉｎ，Ｄｏｘ）对兔脑血管的作用．方法：采用离体兔基底动脉和隐动脉动脉环离体实验方法．结果：多塞平抑制ＫＣｌ４５．６ｍｍｏｌ·Ｌ－１和５羟色胺１０μｍｏｌ·Ｌ－１诱发的兔基底动脉环和隐动脉环收缩，其拮抗ＣａＣｌ２量效反应的ｐＤ２值分别为５．２８±０．４０和４．７６±０．１４（ｎ＝６，Ｐ＜００１）．多塞平５．８μｍｏｌ·Ｌ－１抑制在无Ｃａ２＋液中去甲肾上腺素引起的隐动脉环收缩，多塞平３０μｍｏｌ·Ｌ－１对无Ｃａ２＋液中去甲肾上腺素和恢复正常Ｃａ２＋液（１．２５ｍｍｏｌ·Ｌ－１）引起的隐动脉环收缩均有抑制作用．结论：与隐动脉环相比较，多塞平对基底动脉环具有选择性抑制作用     

多塞平对离体兔基底动脉环和隐动脉环的作用

AIM: To study the effects of doxepin (Dox) on cerebral artery. METHODS: The effects of Dox were observed using the isolated basilar and saphenous artery rings of rabbits. RESULTS: Dox inhibited the constriction of the basilar and saphenous artery rings evoked by KCl with IC50 5.75 mumol.L-1 (95% confidence limits were 2.3-14 mumol.L-1, n = 8) and 34.6 mumol.L-1 (95% confidence limits were 3.8-316 mumol.L-1, n = 8), respectively. Dox also inhibited the constriction of the basilar and saphenous artery rings of the rabbits stimulated by 5-hydroxytryptamine (5-HT), IC50 were 6.3 mumol.L-1 (95% confidence limits were 1.7-23.3 mumol.L-1, n = 7) and 8.0 mumol.L-1 (95% confidence limits were 6.3-10.3 mumol.L-1, n = 6), respectively. In both samples (basilar and saphenous artery rings) CaCl2 evoked, the pD2 of Dox was 5.28 +/- 0.40 and 4.76 +/- 0.14, respectively (n = 6, P < 0.01). Dox 5.8 mumol.L-1 inhibited the constriction of the saphenous artery evoked by norepinephrine (NE) in Ca(2+)-free medium. Dox 30 mumol.L-1 inhibited the constriction of the saphenous artery evoked both by NE and by readmission of CaCl2 (1.25 mmol.L-1). CONCLUSION: As compared with its effect on the saphenous artery, Dox selectively inhibited the basilar artery.     

枸橼酸乙胺嗪对离体豚鼠胸主动脉环的影响

本工作观察了抗丝虫药枸橼酸乙胺嗪（ＤＥＣ）对离体豚鼠胸主动脉环收缩功能的影响。结果显示，ＤＥＣ能显著抑制ＫＣｌ和去甲肾上腺素（ＮＥ）引起的胸主动脉环收缩．使ＫＣｌ和ＮＥ引起的动脉环收缩的剂量效应曲线右移，最大效应降低，均表现为非竞争性拮抗，其ｐＤ＇２值分别为１．９９１和２．２７１。对收缩机制影响研究发现，ＤＥＣ对细胞内Ｃａ２＋释放和外Ｃａ２＋内流均有明显抑制作用。提示ＤＥＣ可能通过其钙拮抗作用影响血管的收缩。     

利多卡因对离体兔胸主动脉环收缩的影响

以维拉帕米(verapamil,Ver)作对照,在离体兔胸主动脉环上对利多卡因(lidocaine,Lid)松弛血管平滑肌的机理进行了探讨。Lid对高K+去极化主动脉环收缩和Ver一样有明显的松弛作用。对去甲肾上腺素(NA)引起主动脉环收缩的试验中,Lid和Ver都能抑制细胞内Ca²⁺的释放,但不抑制外Ca²⁺内流。Lid对KCl,NA量-效曲线产生非平行右移,最大反应压低,且对KCl的抑制作用大于NA,说明Lid对PDC通道有选择性阻滞作用,而对ROC通道相对不敏感。对CaCl₂量-效曲线也产生非平行右移且最大反应压低,呈非竞争性拮抗。初步提示Lid在一定浓度下有拮抗Ca²⁺的作用,这种作用为非特异性,是松弛血管平滑肌机理之一。     

山莨菪碱对离体血管和心房细胞内、外钙影响的研究

山莨菪碱(Ani)能拮抗PE和高K~+所致兔主动脉条收缩,IC_(50)分别为120和86μmol/L,两者比值PE/K~+(IC_(50))=1.39,小于Ver;对5-HT两种收缩成分均有抑制作用;亦能抑制豚鼠左房“静息后增强”和“阶梯现象”;对CaCl_2收缩兔主动脉和豚鼠左房具有非竞争性抑制作用。结果提示,山莨菪碱对细胞外钙经PDC和ROC所致收缩以及由细胞内钙释放诱导的收缩均有拮抗作用。     

牵拉对α1受体激动剂苯肾上腺素诱发兔离体血管收缩反应的影响

目的研究在α1受体激动剂苯肾上腺素(Phe)诱发血管收缩反应实验中,如何确定动脉标本的最适前负荷.方法采用兔离体肾动脉、股动脉、隐动脉、肠系膜动脉、脾动脉和耳中央动脉环标本的等长张力纪录法.结果在1.0～5.0 g前负荷条件下, 随前负荷增加, 各血管环静息张力呈线性增加. KCl (120 mmol·L-1)引起各动脉的收缩随前负荷的增加而增强,但除耳动脉外, 在其他动脉标本上未观察到KCl最大收缩反应的最终坪值点.以Phe(0.01～100 μmol·L-1)为收缩剂时, 在肠系膜动脉, 脾动脉和隐动脉, Phe的EC50(EC50·Phe)值随前负荷增加(1.0～5.0 g)而明显改变; 但是, 各组标本在不同前负荷下的EC50·Phe值中存在一个最小值,其标准差亦很小.结论前负荷明显影响血管的EC50·Phe值测定.确定离体血管标本最适前负荷, 特别是研究受体反应时, 应以受体激动剂的EC50值及其变异程度最小作为关键指标.     

Effects of sub-chronic oral cyanide on endothelial function in rabbit aortic rings

We have investigated how the endothelium affects vascular responses following sub-chronic low dose cyanide administration. Cyanide exists in low levels in cassava foods, which are widely consumed in tropical Africa. Adult rabbits were administered 0.38 mg/kg per day KCN po for 25 days, and responses of the isolated aortic rings to noradrenaline (NA), calcium chloride (Ca2+) and acetylcholine (ACh) were measured in vitro in the presence and absence of the endothelium. In order to establish that the dose was not toxic, animal weight, some haematological indices, plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. Results show that endothelium denudation significantly (P <0.05) attenuates NA-induced contraction in rings from cyanide-treated rabbits. There was a similar reduction in response in Ca2+-depleted NA-precontracted endothelium-denuded aortic rings from cyanide-treated rabbits. Endothelium-denuded rings from cyanide-treated rabbits showed significantly (P <0.05) enhanced relaxation to ACh. In rings from control animals, the responses to NA and Ca2+ were not significantly altered, whether in the presence or absence of the endothelium. There were no significant changes in the studied toxicological indices. We conclude that endothelial compromise is necessary for low-dose sub-chronic cyanide-induced to alter vascular reactivity to NA and ACh.     

四氢小檗碱对离体兔主动脉环的作用和离体豚鼠结肠带平滑肌~(45)Ca内流的影响

THB和Ver相似,对KCl和NE所致兔主动脉环收缩,呈非竞争性拮抗,THB的作用弱于Ver。THB对KCl所致的兔主动脉环收缩的松弛作用,能被20 mmol/L CaCl_2所对抗。 THB,THP和Ver明显抑制80 mmol/L KCl所致的豚鼠结肠带平滑肌细胞的~(43)Ca内流。THB的作用与THP相当,但均弱于Ver。     

氯沙坦对大鼠离体胸主动脉的舒张作用及机制

目的:观察氯沙坦对大鼠胸主动脉的舒张作用,并探讨其作用机制。方法:记录氯沙坦对血栓素A2(TXA2)类似物U46619、氯化钾(KCl)预收缩的离体大鼠胸主动脉环作用,观察N-硝基-L-精氨酸甲酯(L-NAME)与吲哚美辛对其作用的影响。结果:氯沙坦(3×10-8～3×10-5 mol/L)对U46619(1μmol/L)预收缩的主动脉环有内皮依赖性的、浓度依赖性的舒张作用。L-NAME(0.1mmol/L)可显著抑制氯沙坦的舒血管作用。吲哚美辛(1μmol/L)对氯沙坦的舒血管作用无明显影响。氯沙坦对KCl(60mmol/L)诱发的血管收缩无明显影响。结论:氯沙坦对U46619引起的血管收缩有浓度依赖性的舒张作用,此作用具有内皮依赖性,与内皮产生的一氧化氮(NO)有关,与前列环素(PGI2)无关。     

胍法新对保存内皮与去内皮离体大鼠胸主动脉环的作用

本实验观察了选择性较高的α_2受体激动剂胍法新(guanfacine)对离体大鼠胸主动脉环的收缩与舒张作用和对血管组织中cGMP含量的影响。去内皮以及用美兰和血红蛋白预处理均可使胍法新对标本的收缩作用明显增强。对经垂体后叶素预收缩的保存内皮的标本,胍法新有舒张作用。这种作用可因去内皮或用育亨宾处理而消失。胍法新使保存内皮标本组织中cGMP含量明显增加。这些结果提示在大鼠胸主动脉内皮细胞上可能存在着能引起EDRF释放的α_2受体。     

Effects of converting enzyme inhibitors and the calcium antagonist nifedipine alone and in combination on precontracted isolated rabbit aortic rings.

The calcium antagonist nifedipine markedly relaxed intact rabbit aortic rings precontracted with low level potassium chloride while converting enzyme (CE) inhibitors, ramiprilat, enalaprilat, and captopril were only marginally effective. Either CE inhibitor combined with nifedipine, however, significantly accentuated this relaxation. The CE inhibitors increased vascular cyclic GMP content while nifedipine was not active. Thus, inhibition of potassium chloride-induced calcium influx by nifedipine may unmask the vasorelaxant potential of CE inhibitors that in turn may result from local accumulation of endothelium-derived bradykinin.     

西洋参茎叶皂甙对离体家兔胸主动脉条的作用

西洋参茎叶皂甙对离体家兔胸主动脉条的作用吴捷，于晓江，刘传镐（西安医科大学临床药理研究所，西安７１００６１）西洋参茎叶皂甙（ｓａｐｏｎｉｎｓｏｆＰａｎａｘｑｕｉｎｑｕｅ－ｆｏｌｉｕｍｌｅａｆａｎｄｓｔｅｍ，ＳＰＱ）系从西洋参地上部分提取的总皂甙，具有...     

Effects of lysophosphatidylcholine and endothelium on isolated rabbit aortic ring contraction by serotonin

在离体兔胸主动脉环模型上观察溶血性磷脂酰胆碱（ＬＰＣ）促血管收缩作用的机理以及血管内皮对ＬＰＣ促血管收缩作用的影响．１０μｍｏｌ·Ｌ－１ＬＰＣ预温育３０ｍｉｎ可显著增强兔胸主动脉环对５－羟色胺（５－ＨＴ）的收缩反应,使０．１μｍｏｌ·Ｌ－１５－ＨＴ诱导的峰值张力增加到约２．５倍,ＥＣ５０降低,收缩曲线左移．而蛋白激酶Ｃ（ＰＫＣ）抑制剂显形孢菌素（ｓｔａｕｒｏｓｐｏｒｉｎｅ,１００ｎｍｏｌ·Ｌ－１）能抑制ＬＰＣ的促血管收缩作用,ＥＣ５０恢复;去除血管内皮或加入１００μｍｏｌ·Ｌ－１左旋单甲基精氨酸（Ｌ－ＮＭＭＡ）预处理均可显著增强ＬＰＣ的促血管收缩作用,Ｌ－ＮＭＭＡ的作用更强（Ｐ＜０．００１）．结果提示,ＬＰＣ可能通过ＰＫＣ途径促进５－ＨＴ介导的血管收缩,血管内皮可能在其中起调控作用．     

氯通道阻断剂对KCl、5-HT引起的兔脑椎基底动脉血管环收缩效应的影响

目的　探讨不同种类氯通道阻断剂在不同激动剂引起的脑血管平滑肌收缩反应中的作用。方法　记录离体兔脑椎基底动脉环收缩反应。结果　①氯通道阻断剂DIDS、Furosemide及NPPB均浓度依赖性抑制高K+ 及 5 HT引起血管环收缩反应 ,DIDS、Furosemide及NPPB对 5 HT引起收缩的抑制作用明显强于对KCl的作用 ;②在 5 HT引起血管收缩反应中 ,给予SK&F96 36 5引起血管最大舒张的基础上 ,DIDS、Furosemide及NPPB均可引起血管进一步舒张。结论　氯通道可能参与了由高K+ 去极化和 5 HT引起的兔脑椎基底动脉环收缩反应     

The vasorelaxing effect of hydrogen sulfide on isolated rat aortic rings versus pulmonary artery rings

Aim:

To compare the vasorelaxing effects of hydrogen sulfide (H₂S) on isolated aortic and pulmonary artery rings and to determine their action mechanisms.

Methods:

H₂S-induced vasorelaxation of isolated rat aortic versus pulmonary artery rings under 95% O₂ and 5% CO₂ was analyzed. The expression of cystathinonine gamma-lyase (CSE), cystathionine beta synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3MST), SUR2B and Kir6.1 was examined.

Results:

NaHS caused vasorelaxation of rat aortic and pulmonary artery rings in a dose-dependent manner. NaHS dilated aortic rings to a greater extent (16.4%, 38.4%, 64.1%, 84.3%, and 95.9% at concentrations of 50, 100, 200, 500, and 1000 μmol/L, respectively) than pulmonary artery rings (10.1%, 22.2%, 50.6%, 73.6%, and 84.6% at concentrations of 50, 100, 200, 500 and 1000 μmol/L, respectively). The EC₅₀ of the vasorelaxant effect for aortic rings was 152.17 μmol/L, whereas the EC₅₀ for pulmonary artery rings was 233.65 μmol/L. The vasorelaxing effect of H₂S was markedly blocked b y cellular and mitochondrial membrane K_ATP channel blockers in aortic rings (P<0.01). In contrast, only the cellular membrane K_ATP channel blocker inhibited H₂S-induced vasorelaxation in pulmonary artery rings. SUR2B mRNA and protein expression was higher in aortic rings than in pulmonary artery rings. Cystathinonine gamma-lyase (CSE) but not cystathionine beta synthase (CBS) expression in aortic rings was higher than in pulmonary artery rings. 3-Mercapto pyruvate sulfurtransferase (3MST) mRNA was lower in aortic rings than in pulmonary artery rings.

Conclusion:

The vasorelaxing effect of H₂S on isolated aortic rings was more pronounced than the effect on pulmonary artery rings at specific concentrations, which might be associated with increased expression of the K_ATP channel subunit SUR2B.     

麝香保心丸对大鼠离体主动脉环的药理作用

目的：研究麝香保心丸的舒张血管作用及可能的机制。方法：将离体大鼠动脉环随机分成正常组，去内皮组２组（共为６对动脉环，组内比较用自身对照，组间比较用配对对照）。用去甲肾上腺素诱导动脉环收缩后，加入麝香保心丸，记录反应。结果：麝香保心丸对正常组，去内皮组动脉环均有舒张作用（Ｐ＜０．０１），其效应呈剂量依赖；且其对正常组的舒张作用较去内皮组强（Ｐ＜０．０１）。结论：麝香保心丸具有舒张血管的效应，其机制可能有直接及内皮依赖的舒张血管２种作用。