鸟苷对大鼠胸主动脉血管环的舒张作用及机制

目的研究鸟苷对大鼠离体血管环的影响,并探讨其可能的作用机制。方法分离SD大鼠胸主血管环,分成去内皮组和内皮完整组,采用离体血管环实验方法,经生物信号采集与分析系统测定血管环张力的变化,观察鸟苷的舒血管作用并探讨不同抑制剂对鸟苷舒张大鼠离体血管环作用的影响。结果鸟苷(10-9～10-5 mol.L-1)对基础状态下或KCl预收缩血管环的张力无影响;对PE预收缩的血管环有内皮依赖性舒张作用;环氧合酶抑制剂吲哚美辛孵育对鸟苷的舒张作用无明显影响;一氧化氮合酶抑制剂L-NAME或鸟苷酸环化酶抑制剂亚甲蓝可阻断鸟苷的血管舒张作用。结论鸟苷对大鼠离体胸主动脉有浓度依赖性舒张作用,其舒张作用可能与NO-GC-cGMP途径相关。     

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。     

牛磺酸对大鼠胸主动脉的舒张作用及其机制的研究

目的研究牛磺酸舒血管作用的可能机制。方法记录苯肾上腺素(PE)和KCl预收缩的离体大鼠主动脉环张力变化,观察牛磺酸的舒血管作用及不同工具药对其作用的影响。结果牛磺酸(20~80mmol.L-1)对PE(1μmol.L-1)或KCl(60mmol.L-1)预收缩的大鼠主动脉环均有非内皮依赖的、浓度依赖性的舒张作用。在内皮完整的血管环,左旋硝基精氨酸甲酯(0.1mmol.L-1)对牛磺酸的舒血管作用无明显影响;β-丙氨酸(60mmol.L-1)在PE预收缩的血管环增强牛磺酸的舒血管作用,而在KCl预收缩的血管环则降低牛磺酸的舒血管作用;在KCl预收缩基础上,钾通道阻断剂格列本脲(10μmol.L-1)和四乙胺(10mmol.L-1)明显抑制牛磺酸的舒血管作用,而4-氨基吡啶(1mmol.L-1)和BaCl2(1mmol.L-1)无影响。结论牛磺酸有浓度依赖性的血管舒张作用,此作用不依赖血管内皮,可能与其跨细胞膜转运有关,可能有钙依赖性钾通道和ATP敏感性钾通道的参与。     

ARBs预防房颤研究遇挫

房颤是最常见的一种持续性心律失常,发病率和死亡率都很高.抗心律失常药物治疗通常无效,而且可能会导致严重的不良反应,包括室性心律失常.有证据表明,肾素-血管紧张素-醛固酮系统参与了房颤的发生.数据显示,血管紧张素转换酶(ACE)抑制剂以及血管紧张素受体阻滞剂(ARBs)能够预防心房心电生理的改变以及结构的重构.之前的临床研究也表明ACE抑制剂和ARBs可能对房颤有预防作用.其可能的作用机制包括血液动力学、抑制增殖、抗炎症以及抗氧化等作用.     

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。     

苦碟子水提取液对大鼠离体胸主动脉环的舒张作用

目的研究苦碟子的内皮依赖性血管舒张作用,并探讨其可能机制。方法采用大鼠离体主动脉环灌流模型,观察累积浓度苦碟子对基础状态、去氧肾上腺素(PE)和氯化钾(KCl)预收缩的内皮完整血管环和去内皮血管环的舒张作用。结果苦碟子水提取液(苦碟子注射液,相当于含苦碟子原材料0.01～10g.L-1)对基础状态的内皮完整血管环和去内皮血管环的张力无影响。对PE预收缩的内皮完整血管环,苦碟子在累积浓度0.03～10g.L-1呈浓度依赖性舒张作用,分别用一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(0.1mmol.L-1)和鸟苷酸环化酶抑制剂亚甲蓝(10μmol.L-1)预处理,此作用被抑制,用环氧合酶抑制剂吲哚美辛(10μmol.L-1)预处理亦被抑制。对KCl预收缩的内皮完整血管环和对PE或KCl预收缩的去内皮血管环,苦碟子在累积浓度0.01～10g.L-1无明显舒缩作用。结论苦碟子(0.03～10g.L-1)对主动脉具有内皮依赖性舒张作用。该作用可能是通过血管内皮细胞一氧化氮-鸟苷酸环化酶途径和血管内皮细胞环氧合酶途径介导的。     

黄芪的内皮依赖性血管舒缩作用及其机制

目的　黄芪有一定的治疗高血压作用 ,本研究观察其对大鼠离体胸主动脉环舒缩的影响 ,并探讨其可能机制。方法　采用大鼠离体主动脉环灌流模型 ,观察累积浓度黄芪 (0 .0 1～ 10 0g·L- 1)对基础状态、KCl预收缩和去氧肾上腺素 (PE)预收缩的血管环的作用。结果　黄芪 (0 .0 1～ 10 0g·L- 1)对基础状态或KCl预收缩的内皮完整血管环张力无影响。对PE预收缩的内皮完整血管环 ,黄芪在低浓度 (0 .0 1～ 3.0g·L- 1)时呈浓度依赖性舒张作用 ,此作用可被一氧化氮合酶抑制剂左旋硝基精氨酸甲酯(0 .1mmol·L- 1)或鸟苷酸环化酶抑制剂亚甲蓝 (10μmol·L- 1)预处理所抑制 ;而在高浓度 (10～ 10 0g·L- 1)时呈短暂的收缩作用 ,可被内皮素转换酶抑制剂磷阿米酮 (5 μmol·L- 1)预处理所抑制。黄芪对PE预收缩的去除内皮血管环仅呈微弱的浓度依赖性舒张作用。结论　黄芪对主动脉具有内皮依赖性舒缩双相作用。其舒张机制可能为激活血管内皮细胞一氧化氮 鸟苷酸环化酶途径 ;而其收缩机制可能为促进血管内皮合成内皮素。     

川阿格雷钠舒张血管的作用及机制研究

目的:研究川阿格雷钠(MC-002)对大鼠胸主动脉的舒张作用,并探讨其可能的作用机制.方法:测定川阿格雷钠对去甲肾上腺素(NE)和高钾预收缩的大鼠胸主动脉血管环的舒张作用,并观察L硝基精氨酸甲酯(L-NAME)、亚甲蓝、吲哚美辛、格列本脲、蜂毒明肽、氯化钡和4-氨基吡啶对其作用的影响.结果:川阿格雷钠(3～300 μmol/L)能浓度依赖性地舒张NE预收缩的完整血管环,去内皮、亚甲蓝孵育和吲哚美辛孵育均能显著抑制其舒血管作用(P＜0.05,P＜0.01),L-NAME孵育无显著影响.川阿格雷钠拮抗高钾诱导完整血管环收缩的作用被格列本脲(ATP敏感型钾通道KATP抑制剂)和蜂毒明肽(小传导性钙激活型钾通道SKCa抑制剂)显著降低(P＜0.01),氯化钡和4-氨基吡啶无显著影响.川阿格雷钠使NE预收缩的血管平滑肌的钙浓度-收缩曲线下移、右移,且呈现浓度依赖性.结论:川阿格雷钠可能通过内皮细胞的鸟苷酸环化酶途径和环氧合酶途径、开放KATP和SKCa引起平滑肌细胞膜超极化以及减少钙内流而松弛血管.     

血管紧张素受体拮抗剂的真实世界:临床研究证据说明了什么

血管紧张素受体拮抗剂(ARB)在受体水平对肾素-血管紧张素-醛固酮系统(RAAS)发挥抑制作用,因此理论上可能较血管紧张素转化酶抑制剂(ACEI)作用更充分,特别是ARB对血管紧张素(Ang)Ⅱ的阻断作用可能更完全.但上述假设并未获得循证医学证据证实.本文对临床循证研究进行回顾提出,患者在不能耐受ACEI时使用ARB替代治疗可取,但不推荐以ACEI与ARB联合治疗高血压患者.     

粉防己碱的心血管电生理作用

粉防己碱为一源于植物的钙通道阻滞剂,它的心血管电生理作用是:抑制心肌收缩力、张力最大变化速率和自律性,延长功能性不应期;具有负性肌力作用及负性频率作用,而对兴奋性无影响.粉防己碱直接阻滞心肌和血管平滑肌细胞的L型和T型钙电流,但并不移动钙电流的电流-电压曲线,以上作用对其治疗某些心血管疾病是非常有益的.此外粉防己碱还能分别抑制内皮细胞系及血管内皮细胞的 BK_(Ca)和 CRAC通道,此作用可能有助于改变血管内皮细胞的功能活动.     

Sarpogrelate: cardiovascular and renal clinical potential

Sarpogrelate is a selective 5-hydroxytryptamine receptor subtype 2A (5-HT2A) antagonist. It is metabolised to racemic M-1 and both enantiomers of M-1 are also antagonists of 5-HT2A receptors. Sarpogrelate inhibits responses to 5-HT mediated by 5-HT2A receptors such as platelet aggregation, vasoconstriction and vascular smooth muscle proliferation. There is no information available on the pharmacokinetics of sarpogrelate. Sarpogrelate is efficacious in animal models of thrombosis, coronary artery spasm, atherosclerosis, restenosis, peripheral vascular disease, pulmonary hypertension, ischaemic heart disease, myocardial infarction, diabetes and kidney disease. Small clinical trials indicate that sarpogrelate may be beneficial in the treatment of coronary artery disease, angina, restenosis, heart valve prostheses surgery, diabetes mellitus, Raynaud's phenomenon, systemic sclerosis and Buerger's disease. Larger, randomised, double-blind, placebo-controlled clinical trials of sarpogrelate in intermittent claudication, coronary artery disease, restenosis and diabetes should be considered.     

Sarpogrelate: cardiovascular and renal clinical potential

Sarpogrelate is a selective 5-hydroxytryptamine receptor subtype 2A (5-HT_2A) antagonist. It is metabolised to racemic M-1 and both enantiomers of M-1 are also antagonists of 5-HT_2A receptors. Sarpogrelate inhibits responses to 5-HT mediated by 5-HT_2A receptors such as platelet aggregation, vasoconstriction and vascular smooth muscle proliferation. There is no information available on the pharmacokinetics of sarpogrelate. Sarpogrelate is efficacious in animal models of thrombosis, coronary artery spasm, atherosclerosis, restenosis, peripheral vascular disease, pulmonary hypertension, ischaemic heart disease, myocardial infarction, diabetes and kidney disease. Small clinical trials indicate that sarpogrelate may be beneficial in the treatment of coronary artery disease, angina, restenosis, heart valve prostheses surgery, diabetes mellitus, Raynaud’s phenomenon, systemic sclerosis and Buerger’s disease. Larger, randomised, double-blind, placebo-controlled clinical trials of sarpogrelate in intermittent claudication, coronary artery disease, restenosis and diabetes should be considered.     

Therapeutic potentials of sarpogrelate in cardiovascular disease

In view of the pivotal role of serotonin (5-HT) in a wide variety of cardiovascular disorders, extensive effort has been made to develop different types of 5-HT receptor antagonists for therapeutic use. On the basis of experimental studies, this article is focused on the potentials of sarpogrelate, a specific 5-HT2A receptor antagonist as an antiplatelet, antithrombotic, antiatherosclerotic and antianginal agent. The major effects of sarpogrelate are due to the inhibition of 5-HT-induced platelet aggregation and smooth muscle cell proliferation. This agent was found to attenuate the 5-HT-mediated increase in intracellular Ca2+ and ischemia-reperfusion injury in the heart. Sarpogrelate has been found to have beneficial effects in peripheral vascular disease, restenosis after coronary stenting, pulmonary hypertension, acute and chronic myocardial infarction.     

皂苷类成分对血管内皮细胞功能的调节作用研究进展

血管内皮细胞在维持血管生理稳态中发挥了重要的作用,其功能障碍是动脉粥样硬化、冠心病、脑卒中、肿瘤等多种重大疾病发生发展的病理基础,调节血管内皮细胞功能是防治上述疾病的主要途径之一。大量研究表明,皂苷类成分可通过改善血管内皮功能达到治疗疾病的目的。综述了近年来报道的皂苷类成分调节血管内皮功能的研究进展,旨在为皂苷类成分作用机制的阐明和相关重大疾病的防治提供一定参考。     

江门地区季节变化对心脑血管病患者急诊的影响

目的 探索江门地区月份季节对心脑血管病患者急诊的影响。方法对江门市中心医院急诊科2006年7月-2010年6月收治的13685例心脑血管病急诊患者的临床资料进行回顾性调查分析。结果日均心脑血管疾病急诊患者数为7．5人次／天,日均就诊人数在11—12月份较高,为8．1-9．0人次／天,在5-8月份较低,为6．4。6．7人次／天;冠心病就诊人数12月最多,5月最少,冬季明显高于夏季;高血压就诊人数1月最多,6月最少,冬季明显高于夏季;脑梗死就诊人数7月最多,12月最少,夏季明显高于冬季;脑出血1月就诊较高,但和心律失常一样没有明显的季节性。结论江门地区的心脑血管疾病患者的急诊具有一定的季节规律性。     

前列腺素E1在心血管疾病中的应用及不良反应护理干预

查阅近5年内国内外相关文献,对前列腺素E1的药理作用、临床应用及不良反应的护理干预等进行归纳总结。前列腺素E1具有改善血流动力学、抑制血小板聚集、保护血管内皮细胞的作用;治疗冠心病、心力衰竭、风湿性心脏病和先天性心脏病等疗效卓著;常见不良反应有静脉炎、血压下降、胃肠道反应等,有效的护理干预可防治不良反应的发生。     

Pharmacokinetic analysis of antiplatelet effect of sarpogrelate hydrochloride and its application to drug dosage regimen--modeling based on reversible inhibition of 5-HT2 serotonergic receptor in the platelet membrane by sarpogrelate hydrochloride and its metabolite

Sarpogrelate hydrochloride is an antiplatelet drug, and expected to be useful in the treatment of chronic arterial occlusive diseases. Sarpogrelate and its active metabolite (M-1) are potent inhibitors of human platelet aggregation, and selectively inhibit 5-HT2-serotonergic receptors on human platelets. However, the plasma concentrations of these inhibitors do not correlate to the inhibitory effect on platelet aggregation after administration. Sarpogrelate disappears from the plasma more rapidly in comparison to the duration of its pharmacological effect, and the plasma concentration of M-1 is very low (< 1/10 of sarpogrelate). In this paper, we describe a pharmacokinetic-pharmacodynamic model for ascertaining the antiplatelet effects of sarpogrelate and M-1, by considering both the competitive reversible inhibition and the association/dissociation process of these drugs at the 5-HT2 receptors on platelets (Most data used for analysis were obtained from the literatures, except for the serum protein binding rate of M-1). The developed model was well fitted to the actual data, and suggested that M-1 was more effective for the inhibition of platelet aggregation than sarpogrelate. On the basis of these findings, a new method was developed for predicting inhibitory effects on platelet aggregation after oral administration of sarpogrelate hydrochloride. This method is useful for planning a rational dosage regimen of sarpogrelate hydrochloride and predicting the duration of antiplatelet activity after the discontinuance of the drug.     

Current management of peripheral vascular disease: where is the evidence?

The presence of peripheral vascular disease along with coronary heart disease are the two components of generalized atherosclerosis. The risk of having one when the other is present is extremely high. There are four parts to consider in peripheral vascular disease management and these are prevention, plaque stabilization, percutaneous intervention and surgery. Each part has its place but no one would argue that prevention is best when risk is recognized and treated. Classic risk factors and the available diagnostic methods are discussed. Treatment of risk factors is presented with reduction of the low density lipoproteins as the established gold standard during the current era. Procedures of percutaneous vascular intervention with their procedural indications are presented and their advantages and disadvantages discussed. Surgical indications are presented with special indication due to major claudication, rest pain, or tissue loss. Prognosis is also considered and this prognosis is worse in more proximal peripheral vascular disease. Association with other diseases is an important part of prognosis, with the latter especially made worse by the presence of diabetes mellitus. Surprisingly, the long-term prognosis of peripheral vascular disease is worse than that of coronary heart disease. These patients have a significant increase of cardiovascular risk factors and of comorbidities. It has been shown that these patients are undertreated in spite of their high cardiovascular risk. It is mandatory that they receive the same intensive treatment of risk factors as that given to coronary heart disease patients.