四乙酰葛根素对离体大鼠胸主动脉环作用初步研究

目的 观察四乙酰葛根素(Tp)对离体大鼠胸主动脉环的作用以及作用机制。方法 采用大鼠离体胸主动脉环灌流装置,观测四乙酰葛根素对重酒石酸去甲肾上腺素(NA)和氯化钾(KCl)预收缩主动脉环张力的影响。结果 四乙酰葛根素对去甲肾上腺素预收缩主动脉环有明显的舒张作用,与空白对照相比,具有显著性差异(P<0.01);由KCl引起主动脉环预收缩,Tp与空白对照相比,具有统计学差异(P<0.01),对内皮完整血管环的舒张作用明显强于去内皮血管环(P<0.01);Tp对NA在无钙液及正常钙液所致离体血管环收缩的舒张作用不明显(P>0.05)。结论 四乙酰葛根素的舒血管作用与受体依赖性钙通道和电压依赖性钙通道均有关,并且其舒血管作用可能与内皮有一定关系。     

心脉隆注射液对不同状态大鼠离体胸主动脉的影响

摘 要 目的：探讨心脉隆注射液（XML）对不同状态大鼠离体胸主动脉的影响。方法: 采用累积加药法,观察XML对静息、氯化钾（KCl）或去甲肾上腺素（NA）预收缩大鼠离体胸主动脉的影响。使用不同工具药分析作用产生的机制。结果: 与对照组相比,XML在一定浓度范围内可以兴奋静息离体胸主动脉,进一步增加KCl预收缩血管的张力,而降低NA预收缩血管的张力。XML舒张NA预收缩血管的作用可被普萘洛尔、双氯芬酸所抑制,而不受Nω-硝基-L-精氨酸的影响。结论:XML对不同状态下大鼠离体胸主动脉的作用不同,其机制可能与Ca²+通道、β受体和前列腺素有关。     

薰衣草花水煎液对大鼠离体胸主动脉舒张作用机制研究

目的观察薰衣草花提液对大鼠胸主动脉的血管环舒张作用及可能的机制。方法采用离体大鼠胸主动脉环张力测定法。结果①100.0～700.0mg/L的薰衣草花水煎液对内皮完整的血管环的基础张力没有影响。②100.0~700.0mg/L薰衣草花水煎液对KCl(60mmol/L)所致血管收缩没有明显影响,100.0～500.0mg/L的薰衣草花水煎液对去甲肾上腺素(NE,10μmol/L)预收缩的内皮完整血管环产生舒张作用,100.0～700.0mg/L的薰衣草花水煎液对去甲肾上腺素(NE,10μmol/L)预收缩的去内皮血管环产生舒张作用,一氧化氮合酶抑制剂左旋硝基精氨酸甲酯L-NAME(0.1mmol/L)、鸟苷酸环化酶抑制剂亚甲蓝(10μmol/L)预处理后均可明显抑制薰衣草花水煎液的血管舒张作用,环氧化酶抑制剂吲哚美辛(10μmol/L)预处理后不能抑制薰衣草花水煎液的血管舒张作用。③薰衣草花水煎液预处理去除内皮血管环后,能够明显抑制细胞外钙内流所致的血管收缩,但对细胞内钙释放引起的血管收缩没有影响。结论薰衣草花水煎液对血管舒张的作用是部分依赖内皮,部分不依赖内皮,一方面可通过内皮依赖性的NO-cGMP通路产生血管舒张作用,另一方面通过抑制血管平滑肌细胞膜上受体依赖性钙通道产生血管舒张作用。     

四乙酰葛根素对离体大鼠胸主动脉环作用初步研究

目的观察四乙酰葛根素（Tp）对离体大鼠胸主动脉环的作用以及作用机制。方法采用大鼠离体胸主动脉环灌流装置,观测四乙酰葛根素对重酒石酸去甲肾上腺素（NA）和氯化钾（Kcl）预收缩主动脉环张力的影响。结果四乙酰葛根素对去甲肾上腺素预收缩主动脉环有明显的舒张作用,与空白对照相比,具有显著性差异（P〈0．01）;由KCl引起主动脉环预收缩,Tp与空白对照相比,具有统计学差异（P〈0．01）,对内皮完整血管环的舒张作用明显强于去内皮血管环（P〈0．01）;Tp对NA在无钙液及正常钙液所致离体血管环收缩的舒张作用不明显（P〉O．05）。结论四乙酰葛根素的舒血管作用与受体依赖性钙通道和电压依赖性钙通道均有关,并且其舒血管作用可能与内皮有一定关系。     

新结构Rho激酶抑制剂对离体胸主动脉血管环舒张作用及机制研究

目的评价2个全新结构小分子Rho激酶抑制剂J35242和J35243对离体大鼠胸主动脉血管环的舒张作用,并探讨其作用机制。方法利用离体大鼠胸主动脉血管环模型,分别用高浓度KCl和去甲肾上腺素(norepinephrine,NE)预刺激,评价化合物的舒张血管活性;通过各种工具药干预,观察化合物舒张血管作用的内皮相关机制、钾通道相关机制和钙离子相关机制。结果 J35242和J35243可以剂量依赖性舒张高浓度KCl和NE预收缩的血管环,并呈现一定的内皮依赖性;L-NAME和亚甲蓝可在一定程度上影响其舒张作用;化合物还明显抑制由细胞内钙释放和外钙内流引起的血管收缩,说明其可能通过阻断钙离子通道发挥舒张血管作用;另外两个化合物可能不是通过开放钾离子通道发挥舒张血管作用。结论 J35242和J35243在体外具有一定的舒张血管作用,并且J35242的作用要强于J35243,其机制可能依赖于血管内皮功能,另外可能与抑制平滑肌细胞钙离子通道,降低细胞内钙离子浓度相关。     

参麦注射液对大鼠离体胸主动脉血管环的作用及其机制

目的 探讨参麦注射液对大鼠离体胸主动脉血管环的作用及其机制。方法采用离体血管灌流方法，观察参麦注射液对血管环的直接作用；对苯肾上腺素(PE)或氯化钾(KCl)所引发血管收缩作用的影响；对内钙释放和外钙内流所引发血管收缩作用的影响；对乙酰胆碱(ACh)所引发血管舒张作用的影响。结果参麦注射液对血管环无明显的直接作用；对PE和KCl引发的收缩均有明显的抑制(P＜0.05或＜0.01)；对内钙释放和外钙内流所引发收缩作用均有明显的抑制(P＜0.01)；对ACh所引发的舒张作用有明显的抑制(P＜0.05或＜0.01)。结论参麦注射液既能抑制PE和KCl对血管环所引起的收缩作用，又能抑制ACh对血管环所引起的舒张作用，有双向调节血管张力的作用。     

黄芩苷对离体大鼠胸主动脉的舒张作用及机制

研究黄芩苷对大鼠离体胸主动脉环的舒张作用并探讨其可能的机制。记录去甲肾上腺素(NE)和KCl预收缩的大鼠离体主动脉环张力变化,观察黄芩苷的舒血管作用及不同工具药对其影响。实验发现黄芩苷对NE和KCl引起的去内皮和内皮完整大鼠胸主动脉环的收缩均有舒张作用;L-硝基精氨酸甲酯、亚甲蓝不能抑制黄芩苷对大鼠胸主动脉环的舒张作用,吲哚美辛能显著抑制;钾离子通道阻断剂4-氨基吡啶、四乙基胺、BaCl2不能抑制黄芩苷对胸主动脉环的舒张作用,格列苯脲能抑制黄芩苷的舒张作用;无钙环境下,黄芩苷预处理对NE收缩有明显抑制作用。因此,黄芩苷具有浓度依赖性血管舒张作用,此作用具有内皮依赖性和非内皮依赖性特点,内皮依赖性收缩可能与前列环素途径有关,非内皮依赖机制可能与KATP通道及钙离子通道有关。     

阿托品对大鼠肠系膜动脉的舒张作用及机制

目的研究阿托品的扩血管作用及机制。方法以大鼠肠系膜动脉为标本，考察阿托品对去甲肾上腺素(NE)预收缩血管的舒张作用以及血管内皮细胞、血管平滑肌在该效应中的作用。结果阿托品能显著舒张NE预收缩的完整内皮血管，去内皮后该作用明显降低。L-N^ω-硝基精氨酸甲酯、吲哚美辛、普萘洛尔及格列本脲对阿托品的舒张作用无明显影响。阿托品对KCl的量效曲线及咖啡因缩血管作用均无明显影响，但能浓度依赖性地抑制NE诱导的内钙释放以及经受体操纵性钙通道的外钙内流。结论阿托品有明显的扩血管作用，其通过抑制受体介导的外钙内流和内钙释放而舒张血管。     

复方夏枯草活性部位对离体大鼠胸主动脉的舒张作用及机制研究

摘 要 目的： 探讨复方夏枯草活性部位（AFCP）对大鼠离体胸主动脉的作用及其可能的机制。方法: 采用离体大鼠胸主动脉张力实验,经生物信号采集与分析系统测定血管环张力的变化,观察AFCP的舒张血管作用。结果:AFCP（100～500 μg·ml^-1）能显著降低苯肾上腺素（PE,1 μmol·L^-1）引起的血管收缩,对内皮完整和去内皮血管均有（75%±8%）舒张作用。AFCP的舒血管作用不受一氧化氮合酶抑制药L NNA、岛苷酸环化酶抑制药MB、钾通道阻滞药TEA和格列苯脲的影响。在无钙K-H 液中AFCP（300 μg·ml^-1）可使 CaCl₂ 的量效曲线下移且使PE的最大收缩幅度降低。结论: AFCP够浓度依赖性舒张大鼠胸主动脉,其舒张血管作用无内皮依赖性。其作用机制可能与抑制细胞内钙离子释放和细胞外钙离子内流有关,与NO途径、前列环素生成和钙激活的钾通道无关。     

黄酮类化合物WX-02对兔离体血管环的舒张作用

目的探讨黄酮类化合物WX-02对兔离体血管环的舒张作用及其作用机制。方法采用兔离体血管环灌流方法,记录WX-02对去甲肾上腺素(norepinephrine,NE)、氯化钾(KCl)收缩的血管环的舒张作用;观察WX-02的舒张作用与内皮的关系;比较WX-02(0.1、0.3mmol·L-1)孵育后CaCl2累积收缩量效曲线的变化及由NE引起的依赖于细胞内钙和外钙收缩反应的变化。结果浓度为0.03¹.0mmol·L-1 WX-02能舒张由致痉剂高钾、去甲肾上腺素引起的收缩;内皮不影响WX-02的舒张作用;浓度为0.1、0.3mmol·L-1 WX-02均能使CaCl2累积收缩量效曲线右移,低浓度的WX-02可能抑制细胞内钙外流,而高浓度的WX-02抑制细胞内钙外流和外钙内流。结论WX-02能够浓度依赖性的舒张血管平滑肌,其作用机制与内皮无关,与阻断不同的钙通道有关。     

藻酸双酯钠对大鼠离体胸主动脉的血管收缩作用

目的探讨藻酸双酯钠(ASD)引起心绞痛等副作用是否由其对血管的直接效应所致,并探讨其可能机制。方法采用大鼠离体血管环标本浴管内实验,观察累积浓度ASD(0.05～500mg.L-1)对血管环的作用。结果在内皮完整血管环,ASD对基础状态或KCl预收缩血管环的张力无明显影响;对去氧肾上腺素(PE)预收缩的血管环,ASD在低浓度时无明显作用,高浓度时具有收缩作用。而在PE预收缩的去内皮血管环上,ASD0.05～500mg.L-1对血管环的张力均无明显影响。内皮素转换酶抑制剂磷阿米酮和环氧化酶抑制剂吲哚美辛预孵育对PE预收缩血管环的ASD收缩作用无明显影响,血管紧张素转换酶抑制剂卡托普利预孵育可部分抑制ASD的血管收缩。ASD(500mg.L-1)对PE预收缩血管环的乙酰胆碱血管舒张效应无明显影响。结论高浓度ASD对胸主动脉具有内皮依赖性收缩作用,其机制可能部分与促进血管紧张素Ⅱ的合成和(或)激活有关。     

参麦注射液对大鼠离体胸主动脉血管环作用及机制的研究

目的 探讨参麦注射液对离体大鼠胸主动脉血管环的作用及作用机制.方法 采用离体血管灌流方法,观察参麦注射液对血管环的直接作用;对苯肾上腺素(PE)或氯化钾(KCl)所引发收缩作用的影响;对内钙释放和外钙内流所引发收缩作用的影响;对乙酰胆碱(ACH)所引发舒张作用的影响.结果 参麦注射液对血管环无明显的直接作用(与对照组比较P均＞0.05);对PE和KCl引发的收缩均有明显的抑制(与对照组比P＜0.05);对内钙释放和外钙内流所引发收缩作用均有明显的抑制(与对照组比较P均＜0.01);对ACH所引发的舒张作用有明显的抑制(与对照组比较P均＜0.05).结论 参麦注射液既能抑制PE和KCl对血管环所引起的收缩作用,又能抑制ACH对血管环所引起的舒张作用,有双向调节血管张力的作用.     

Puerarin protects against high glucose-induced acute vascular dysfunction: Role of heme oxygenase-1 in rat thoracic aorta

ObjectiveTo investigate the antioxidant and vascular protective effect of puerarin, an isoflavone glycoside known in traditional Chinese medicine on vascular reactivity subsequent to high glucose stress.MethodsThe thoracic aortic rings with or without endothelium from male SD rats were mounted in an organ bath. Isometric contraction of aortic rings was measured. HO-1 protein expression and HO activity were also evaluated.Results(1) After incubation with 44 mmol/L of high glucose for 2 or 4 h, the vascular contraction responses to phenylephrine (PE) and relaxation response to acetylcholine (Ach) decreased in an endothelium-dependent manner; (2) Coincubation with puerarin (10^? 10–10^? 8 mol/L) and high glucose, the high glucose-induced vasoconstriction and vasodilation dysfunction was partly inhibited in a dose-dependent manner; (3) Puerarin increased the HO-1 protein expression and HO activity of thoracic aorta. ZnPP (an inhibitor of heme oxygenase-1) offset the protective effect of puerarin.ConclusionPuerarin could alleviate the high glucose-induced acute endothelium-dependent vascular dysfunction in rat aortic rings. HO-1 activity was proposed as a mechanism to account for the protection of vascular responses by puerarin.     

度洛西汀对大鼠胸主动脉环舒张功能的影响

目的研究度洛西汀(DLX)对血管舒张功能的影响并探讨其作用机制。方法采用离体血管环灌流装置,观察DLX对大鼠胸主动脉环的作用及不同工具药的影响。结果 DLX对KCl(30 mmol.L-1)和NE(1μmol.L-1)预收缩的血管环具有浓度依赖的舒张作用,对内皮完整和去内皮血管环舒张作用无差异,该舒张作用为非内皮依赖性。在KCl预收缩基础上,加入钾通道阻断剂格列苯脲Gli(10μmol.L-1)、四乙胺TEA(10 mmol.L-1)、氯化钡BaCl2(1 mmol.L-1)、四氨基吡啶4-AP(1 mmol.L-1)和5-HT2受体阻断剂赛庚啶(1μmol.L-1)均不能抑制DLX的舒血管效应;α1受体阻断剂哌唑嗪(1μmol.L-1)组对DLX舒血管作用有抑制作用。在无钙液中,DLX可以明显抑制NE和CaCl2收缩血管的作用。结论 DLX能够浓度依赖性的舒张血管,其机制可能与抑制经由血管平滑肌细胞膜VDC和ROC通道的钙离子内流,拮抗α1受体以及抑制胞质内钙离子释放有关。     

儿茶酚抑素对大鼠离体血管环张力的影响

目的研究儿茶酚抑素(CST)对大鼠离体血管环的效应及其可能的机制。方法记录苯肾上腺素(PE)预收缩的大鼠离体胸主动脉环张力变化,观察不同浓度CST的作用效果以及应用L-硝基-精氨酸甲酯(L-NAME)抑制一氧化氮(NO)生成后的作用效果的变化。结果①PE(10-9～10-5mmol/L)对大鼠离体血管环有浓度依赖性的收缩作用;②CST在10-8～10-4mol/L浓度范围内对PE(10-6mmol/L)引起的血管收缩有浓度依赖性的舒张作用,其舒张作用较同等浓度的乙酰胆碱(Ach)和硝普钠(SNP)均弱;③用L-NAME(10-4mol/L)预处理后,CST的作用明显减弱。结论 CST对PE诱发的血管收缩有浓度依赖性的舒张作用,血管内皮释放的NO可能是CST的作用途径之一。     

Mechanisms underlying vasorelaxant action of astragaloside IV in isolated rat aortic rings

1. Astragaloside IV is a component from the widely used traditional Chinese herb Astragalus membranaceus and its effect on rat aortic ring contraction and relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was isolated in an organ bath and ring tension was recorded with or without endothelium. Cumulative effects of astragaloside IV on vessel contraction and relaxation were observed in the presence of various antagonists related to vessel activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel contraction induced by phenylephrine and potassium chloride. The amount of calcium released from intracellular stores sensitive to phenylephrine was also markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in endothelium-intact rings, which was partly inhibited by pre-incubation with nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Astragaloside IV also induced a significant increase in aortic tissue content of guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro. Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation, whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV inhibited vessel contraction through blocking calcium influx and intracellular calcium release. The endothelium-dependent vessel dilation of astragaloside IV was attributed mainly to the endothelium-dependent NO-cGMP pathway.     

Vasorelaxant effect of formononetin in the rat thoracic aorta and its mechanisms

The purpose of the present study was to investigate the effect of formononetin and the related mechanisms on isolated rat thoracic aorta. Formononetin concentration dependently relaxed aortic rings precontracted with norepinephrine (NE, 1 μM) or KCl (80 mM). Pretreatment with formononetin noncompetitively inhibited contractile responses of aortas to NE and KCl. The vasorelaxant effect of formononetin partially relied on intact endothelia, which was significantly attenuated by incubation with N(ω)-nitro-L-arginine methyl ester (100 μM). In endothelium-denuded rings, glibenclamide (10 μM) and tetraethylammonium (5 mM) showed slight reduction in the vasorelaxant effect of formononetin. Moreover, formononetin reduced NE-induced transient contraction in Ca2?-free solution and inhibited the vasocontraction induced by increasing external calcium in medium plus 80 mM KCl. Our results suggested that formononetin induced relaxation in rat aortic rings through an endothelium-dependent manner via nitric oxide synthesis pathway, and also involving an endothelium-independent vasodilatation by the blockade of Ca2? channels. The opening of K? channels might also be one of the mechanisms of formononetin-induced vasorelaxation.     

Isometric contraction increases endothelial nitric oxide synthase activity via a calmodulin antagonist-sensitive pathway in rat aorta

In this work, the possibility that isometric contraction activates endothelial nitric oxide synthase (eNOS) in a calcium/calmodulin (Ca2+/CaM)-dependent manner was examined in rat thoracic aorta. Step-wise stable contractile responses (precontractions) to phenylephrine were obtained in endothelium-intact and endothelium-denuded aortic rings. The subsequent addition of the NO synthase inhibitor, N(G)nitro-l-arginine methyl ester (l-NAME), or the soluble guanylyl cyclase inhibitor, ODQ, further augmented precontractions in a concentration-dependent manner. The amplitude of l-NAME- and ODQ-induced increases in tone were dependent on the level of precontraction; the maximal increments for l-NAME and ODQ were observed in arteries precontracted with phenylephrine at 67% of its maximal effect. Likewise, in endothelium-intact non-contracted arteries, l-NAME and ODQ induced small but significant increases in tone. Neither l-NAME nor ODQ had any effect in endothelium-denuded preparations. In endothelium-intact aortic rings precontracted with high K+ solutions, l-NAME also elicited supplementary contractions dependent on precontraction level. The CaM antagonist, calmidazolium, inhibited in a concentration-dependent, noncompetitive, manner the effects of l-NAME on the tone of endothelium-intact phenylephrine-precontracted aortic rings. These results suggest that isometric contraction increases the activity of eNOS by means of the Ca2+/CaM complex in rat aorta.     

山楂总黄酮对大鼠离体血管功能的影响及其机制

目的研究山楂总黄酮对大鼠离体血管功能的影响,并初步探讨其作用机制。方法采用大鼠离体血管灌流模型,观察山楂总黄酮对大鼠离体血管舒张和收缩功能的影响。结果山楂总黄酮时大鼠离体血管具有浓度依赖性地舒张作用,还可浓度依赖性地抑制苯肾上腺素、CaCl2：引起的血管收缩,对无钙液中肾上腺素引起的血管收缩也有抑制作用。非选择性钾通道抑制剂、内向整流钾通道抑制剂可部分阻断山楂总黄酮引起的血管舒张作用。结论山楂总黄酮对大鼠离体血管具有舒张作用,该作用主要是通过抑制细胞外Ca＾2＋内流,抑制细胞内贮Ca＾2＋释放,以及激活非选择性钾通道和内向整流钾通道来实现的。     

Effects of vitamin D3 derivative – calcitriol on pharmacological reactivity of aortic rings in a rodent PCOS model

BackgroundThe aim of this study was to examine the effects of the hyperandrogenic state in dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS), the vascular responses to different vasoactive agents, and the modulatory role of vitamin D₃.MethodsAPCOS model was induced by DHT application in 20 femaleWistar rats. Ten of the DHT treated rats simultaneously received calcitriol treatment. After 10 weeks, myographs were used to test the reactivity of isolated thoracic aortic rings to norepinephrine and acetylcholine. Thereafter, the vascular rings were incubated with the NO-synthase blocker (nitro-L-arginine methyl ester) or the cyclooxygenase inhibitor (indomethacin) for 20 min, and the effects of norepinephrine and acetylcholine were re-evaluated.ResultsNorepinephrine-induced vasoconstriction was enhanced after DHT treatment, but this effect was attenuated by calcitriol administration. Vasorelaxation of DHT-treated thoracic aortic rings was impaired, but this could be partly reversed by calcitriol application. Impaired NO-dependent vasorelaxation in DHT-treated animals was mostly reversed by concomitant calcitriol administration, but this effect was diminished by prostanoid-dependent vasoconstriction.ConclusionsThese studies show that the enhanced sensitivity to vasoconstrictors and impaired NO-dependent vasorelaxation in hyperandrogenic PCOS rats could be partially reversed by calcitriol treatment.