粉防己碱抑制豚鼠离体气道C神经纤维兴奋引起的收缩(英文)

目的:研究粉防己碱(Tet)对豚鼠离体气管/支气管的感觉神经C纤维兴奋的抑制作用.方法:记录电场刺激所致的C纤维兴奋所产生的标本收缩(phase Ⅱ)张力,了解Tet的作用.结果:Tet 0.3—30 μmol·L~(-1)抑制phase Ⅱ收缩,在气管/支气管上,Tet 1 μmol·L~(-1)的抑制率分别是:40±38％和75±22％;用氯苯那敏或阿托品作用后,Tet 1 μmol·L~(-1)的抑制率分别是70±16％和64±16％;Tet不抑制外源性P物质引起的标本收缩.结论:Tet 1μmol·L~(-1)抑制豚鼠离体气道收缩的机理与其抑制感觉神经C纤维兴奋释放神经肽的作用有关.     

内皮素-1对离体豚鼠工作心脏的作用

在离体豚鼠工作心脏模型上,单次推注内皮素-1(ET-1·30,90,300pmol·L~(-1))能引起初始短暂的正性肌力作用及随后持续的负性肌力,负性频率作用。低剂量的ET-1(30,90,pmol·L~(-1))能使心脏各功能指标可逆性恢复.而高剂量的ET-1(300pmol·~(-1))则强烈收缩冠脉,造成心肌缺血,LDH值升高,最终导致心功能指标显著受抑。环氧化酶抑制剂In-domethacin 30 μmol·L~(-1)能显著增强ET-l收缩冠脉血管的作用,加重心肌缺血。上术结果表明:ET-1通过强烈收缩冠脉血管,造成心肌缺血而引起离体豚鼠工作心脏心功能的抑制。并提示PGI_2能显著拮抗ET-1的缩血管作用。     

蜂毒肽对离体豚鼠心房的双向作用(英文)

目的:研究蜂毒肽(Mel)对离体豚鼠心房的作用。方法:累积浓度法测定Mel给药前后左房收缩幅度及右房频率,观察量效曲线及时效曲线。观察钙离子通道阻滞剂Ver对Mel作用的影响。结果:低浓度Mel(0.1-0.8μmol·L~(-1))对左心房产生正性肌力作用;高浓度Mel(1.6-12.8μmol·L~(-1))产生负性肌力作用。Mel对右心房产生正性频率作用。Mel的双向作用可被Ver 0.3μmol·L~(-1)压低。结论:Mel对离体豚鼠左心房收缩具双向作用,对右心房具正性频率作用。Mel对左心房收缩的双向作用可被Ver压低,提示Mel对心房的作用可能通过电压依赖性钙通道。     

牛磺酸对豚鼠乳头状肌慢反应动作电位的影响(英文)

目的:研究牛磺酸对豚鼠乳头状肌慢反应动作电位的影响.方法:高钾(24 mmol·L~(-1))或河豚毒素(40 μmol·L~(-1))诱发慢反应动作电位.哇巴因诱发振荡后电位.结果:牛磺酸(20mmol·L~(-1))减少V_(max),延长APD_(50)并拮抗氯化钙(3 mmol·L~(-1))增加APA和V_(max)及缩短APD的作用,增加哇巴因诱发OAP所需浓度并延长其发生时间.结论:牛磺酸有钙拮抗剂的性质     

内皮舒张因子抑制剂对低氧收缩离体猪冠脉的影响(英文)

左旋硝基精氨酸,NLA (0.2 mmol·L~(-1))可阻断离体猪冠脉依内皮性缺氧收缩反应,用左旋精氨酸,L-Arg(2mmol·L~(-1))预处理可显著降低NLA的抑制作用,四乙胺,TEA(10mmol·L~(-1))和格列本脲,Gli(1 μmol·L~(-1))对缺氧收缩反应无明显影响,而Cro-makalim,Cro(1 μmol·L~(-1))则可抑制缺氧冠脉收缩。     

卡马西平增强γ-氨基丁酸对大鼠脑片的作用(英文)

目的:研究卡马西平(Car)对γ-氨基丁酸(GABA)在海马区域作用的影响.方法:在海马脑片(350μm)上刺激(0.5 Hz,50μs)Schaffer氏纤维,记录CA1区锥体细胞的诱发场电位.结果:Car 0.2mmol·L~(-1)对CA1区锥体细胞的诱发场电位没有明显影响,但Car 0.2 mmol·L~(-1)和GABA(0.1-1 mmol·L~(-1))同用抑制场电位作用比单用GABA时显著增强.Bicuculline不能翻转被Car加强的GABA的抑制作用.继而,左旋巴氯芬抑制场电位作用强于GABA.Car 0.2 mmol·L~(-1)和左旋巴氯芬(1-5μmol·L~(-1))同用抑制场电位作用比单用左旋巴氯芬时显著增强.结论:Car增强GABA对海马CA1区锥体细胞的抑制作用,其作用机制可能与GABA_B受体有关.     

胍丁胺对异丙肾上腺素诱发豚鼠乳头状肌后除极的影响(英文)

目的:研究胍丁胺(Agm)对异丙肾上腺素(Iso)诱发豚鼠乳头状肌早发和晚发后除极(EAD和DAD)的影响及其作用机制。方法:细胞内玻璃微电极技术。结果:(1)Agm明显抑制Iso诱发的EAD和DAD;(2)预先应用NOS抑制剂L-NAME0.5mmol·L~(-1),不能影响Agm1.0mmol·L~(-1)对Iso 20nmol·L~(-1)诱发EAD和DAD的抑制作用;(3)预先应用咪唑啉受体(IR)和肾上腺素能α_2受体(α_2-AR)拮抗剂idazoxan 0.1mmol·L~(-1)则可阻断这种作用。结论:Agm对Iso诱发EAD和DAD的抑制作用由α_2-AR和/或IR介导,并与钙内流减少有关。     

3-Morpholinosydnonimine-N-ethylcarbamide对缺氧诱发离体猪冠脉机械和电反应的影响(英文)

研究3-Morpholinosydnonimine-N-ethylcarbamide(SIN-1)对缺氧诱发离体猪冠脉机械和电反应的影响.方法:同步记录机械张力和膜电位.结果:缺氧可诱发离体猪冠脉平滑肌细胞膜去极化和收缩;SIN-1(100 μmol·L~(-1))和维拉帕米(Ver,10 μLmol·L~(-1))可使其复极化和松弛.SIN-1和Ver还可抑制左旋硝基精氨酸(NLA,0.2 mmol·L~(-1))和KCl(40mmol·L~(-1))诱发的离体猪冠脉去极化和收缩反应.结论:缺氧收缩离体猪冠脉是其抑制一氧化氮释放、增加Ca~(2 )内流的结果.     

花椒毒酚对豚鼠离体心房肌生理特性的影响

目的 :研究花椒毒酚对豚鼠离体心肌生理特性的影响。方法 :采用豚鼠离体心房 ,测定花椒毒酚对豚鼠心房率 ,心肌收缩力 ,左心房的兴奋性的影响。结果 :在心肌收缩力的实验中 ,给花椒毒酚 2 0 ,4 0 ,80 μmol·L-115min后 ,左心房的收缩力分别为0 .85、0 .6 8、0 .4 8g ,与对照组比较 ,花椒毒酚明显抑制豚鼠左心房肌的收缩力 (P <0 .0 5 ) ,并呈浓度依赖性 ;在对心房率的实验中 ,给花椒毒酚 2 0 ,4 0 μmol·L-1,30min后 ,离体右心房的频率从90 .0次·min-1分别下降至 6 0 .2、38.7次·min-1,与对照组比较有显著的统计学意义 (P <0 .0 5 ) ;花椒毒酚对豚鼠左心房的功能性不应期和左心房兴奋性无明显影响。结论 :花椒毒酚可以降低心房自律性、抑制心房收缩力 ,其负性变频和负性变力效应可能与其抑制心肌细胞外钙内流和内钙释放有关。     

4-[4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基]-4′-去甲表鬼臼毒素在荷肉瘤180小鼠体内的药物动力学(英文)

目的:研究4-[4″-(2″,2″,6″,6″-四甲基哌啶氮氧自由基)氨基]-4′-去甲表鬼臼毒素在荷肉瘤180小鼠体内的药物动力学.方法:用HPLC紫外检测法.结果:GP-7在小鼠血浆中的浓度—时间过程符合二室开放模型.20,60mg·kg~(-1)iv,T_((1/2β)约40 min;药物浓度以肝脏和肺中最高;肿瘤组织中药物水平高于脾,肾和骨髓.72 h内,经尿以原形排出的GP-7占给药量的20％左右.结论:GP-7在荷肉瘤180在小鼠体内分布较广,消除较慢.肿瘤组织中浓度较高,部分以原形从尿中排出.     

呋喃二氢吡啶Ⅰ对豚鼠心肌收缩力及动作电位的影响

呋喃二氢吡啶I(FDP I)呈浓度依赖性地抑制豚鼠心肌收缩力,IC_(50)为1.62μmol·L~1,并能抑制心肌静息后增强效应.成对刺激及正阶梯现象的收缩幅度,离体心乳头状肌细胞跨膜电位实验表明:FDPI 1.0、4.0μmol·L~1能缩短动作电位之APD_(30)·APD_(50),APD_(90),硝苯碇(Nif)0.1.1.0,4.0μmol·L~1亦能缩短APD,但两药在所试浓度范围内,对APA和V_(max)均无明显影响。     

Inotropic and chronotropic profile of MCI-154: comparison with isoproterenol and imazodan in guinea pig cardiac preparations.

Although recent studies indicate that MCI-154 exerts novel positive inotropic actions in heart muscle, the chronotropic properties of this new drug remain undefined. The present study compared the inotropic/chronotropic profile of MCI-154 with those of a nonselective beta 1/beta 2-agonist (isoproterenol, Iso) and a type III phosphodiesterase inhibitor (imazodan, CI-914) in cardiac preparations isolated from guinea pigs. The inotropic efficacy of MCI-154 was approximately equal to that of Iso and CI-194 in electrically paced (1 Hz) atrial muscle, with each agent increasing isometric contractile tension approximately 170% above basal (predrug) values. The inotropic EC50 for Iso (2.9 +/- 0.7 x 10(-9) M) was several orders of magnitude less than that for MCI-154 (1.4 +/- 0.4 x 10(-4) M) and CI-914 (1.1 +/- 0.2 x 10(-4) M). The inotropic potency of MCI-154 was equivalent in atrial and left ventricular myocardium. Both Iso and CI-194 substantially increased spontaneous beating frequency of sinoatrial preparations, and the inotropic/chronotropic potency ratio for each was unity. In contrast, MCI-154 exerted a slight negative chronotropic action on basal sinoatrial rate. Moreover, the negative chronotropic influence of MCI-154 was increased several-fold in the presence of Iso-stimulated maximal increases in heart rate (HR), and this inhibitory chronotropic action of MCI-154 was not prevented by muscarinic receptor blockade with atropine. These findings indicate that MCI-154 has a unique inotropic/chronotropic profile in cardiac tissues of guinea pigs in that this drug (a) efficaciously increased myocardial contractility, (b) had minimal effect on basal sinoatrial automaticity and yet (c) markedly inhibited sympathetically mediated sinus tachycardia.     

柳珊瑚酸钠对豚鼠离体工作心脏及其缺血再灌注血流动力学的影响(英文)

目的:研究柳珊瑚酸钠(suberogorgin,Sub)对正常和缺血再灌注损伤工作心脏的作用.方法:用含edetic acid 0.2 μmol·L~(-1)的克-亨氏液(37±0.5 C)从左肺静脉对心脏进行灌注.左房灌注压和左室负荷分别为1.0和7.2kPa,50 min低流缺血期间,冠脉流量为正常灌注时的4.7±0.2％,此后进行35 min的再灌注.结果:Sub 10 μmol·L~(-1)使正常工作心脏的AP,LVSP, dp/dt_(max),-dp/dt_(max),CO和SV分别提高14％,17％,17％,22％,15％和32％,但使LVEDP和HR各下降200％和11％;Sub 50 μmol·L~(-1)则降低上述指标.对于缺血再灌注损伤的心脏,Sub 10 μmol·L-1使除HR外的上述指标恢复至缺血前水平,而Sub 50 μmol·L~(-1)仅使这些指标部分恢复.结论:Sub对心肌缺血再灌注损伤有明显的保护作用.     

强心扩血管药羟苯氨酮对离体心肌与血管的作用

为阐明强心扩血管药羟苯氨酮对心肌与血管的直接影响,采用离体心脏,离体心肌与血管制备,以心肌张力、心率、冠脉流量及血管平滑肌张力为观察指标。结果显示:给离体大鼠心脏灌流羟苯氨酮0.1～1μmol·L^-1可使心肌收缩力和冠脉流量明显增加,心率轻度减慢。羟苯氨酮剂量依赖性地增加豚鼠乳头肌和左房肌张力,并减慢右房频率。羟苯氨酮(1～50μmol·L^-1)非竞争性地对抗KCl,5-HT和CaCl₂致狗冠状动脉,基底动脉和肠系膜动脉的收缩,显示它有松弛血管平滑肌的作用。与磷酸二酯酶抑制剂类药物米力农作比较,两者的正性肌力作用与扩血管作用相似。然而,羟苯氨酮减慢心搏频率,米力农则增加心率。提示羟苯氨酮有直接正性肌力、负性频率与扩血管作用。     

Effects of [Na] and [Ca] on the responses to milrinone in rat cardiac preparations

In the present investigation we have studied the influence of changing the [Ca²⁺] and [Na⁺] on the cardiac responses to milrinone in various preparations of rat heart. Milrinone (5 × 10⁻⁵ to 8 × 10⁻⁴ M) produced a dose-dependent positive chronotropic effect on right atrium and a positive inotropic effect on left atrium and papillary muscle of the rat. A decrease in [Ca²⁺] (from 2.2 to 1.1 mM) or an increase in [Na⁺] (from 120 to 60 mM) increased the milrinone-induced inotropic effect in left atrium and papillary muscle. However, in right atrium the chronotropic effect of milrinone was significantly decreased under these conditions. Opposite changes to milrinone-induced responses were observed when [Ca²⁺] was increased (to 3.3 mM) or when the [Na⁺] was decreased to 60 mM. Nifedipine (3 × 10⁻³ M), a selective Ca²⁺ channel blocker, significantly inhibited the chronotropic response to milrinone in right atrium. However, the inotropic response to milrinone was found to be significantly greater in the presence of nifedipine. A veratridine-induced positive inotropic effect in the left atrium was also significantly increased in the presence of nifedipine. Tetrodotoxin (TTX, 1 × 10⁻⁶ M), a fast sodium channel blocker, significantly reduced the inotropic response to milrinone in left atrium and papillary muscle. A milrinone-induced dose-dependent increase in the baseline tension was observed in the right atrium which was abolished in low [Ca²⁺] and significantly increased in high [Ca²⁺]. Our data suggest the possibility that milrinone increases Ca²⁺ influx in the right atrium to cause the chronotropic effect. Milrinone also may possess an action like veratridine, involving an increased influx of Na⁺ through fast Na⁺ channels in left atrium and papillary muscle, and this action is possibly involved in the positive inotropic effect.     

A Na+/Ca2+ exchanger inhibitor, KB-R7943, caused negative inotropic responses and negative followed by positive chronotropic responses in isolated, blood-perfused dog heart preparations

Effects of a Na+/Ca2+ exchanger inhibitor, KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl] isothiourea methanesulfonate), on the sinoatrial nodal pacemaker activity, atrial contractility and ventricular contractility were investigated in the isolated and blood-perfused right atrium and left ventricle of the dog. KB-R7943 (0.03- 3 micromol) induced negative inotropic effects and negative followed by positive chronotropic effects in the right atrium and negative inotropic effects in the left ventricle. Neither atropine nor hexamethonium affected the cardiac responses to KB-R7943. Propranolol attenuated the positive chronotropic response to KB-R7943 but imipramine did not. Tetrodotoxin potentiated the positive chronotropic response to KB-R7943 in 6 of 11 isolated atria. When NaCl infusion increased atrial contractile force and atrial rate, KB-R7943-induced negative inotropic and chronotropic responses were attenuated in a dose-dependent manner. CaCl2 infusion potentiated the negative chronotropic response to KB-R7943 but did not affect the inotropic response significantly. On the other hand, ouabain (17 nmol) attenuated the negative inotropic response, but not chronotropic response, to KB-R7943. These results suggest that KB-R7943-induced cardiac effects relate to the Na+ activity, probably mediated through the Na+/Ca2+ exchanger, and the Na+/Ca2+ exchanger modifies the pacemaker activity and myocardial contractility in the dog heart.     

Effects of 1-(2-chloro-4-hydroxyphenyl)-t-butylaminoethanol (HOKU-81), a new bronchodilator, on isolated trachea and atria of guinea pig

Effects of 1-(2-chloro-4-hydroxyphenyl)-2-t-butylaminoethanol hydrochloride (HOKU-81), one of the metabolites of tulobuterol, on isolated trachea and atria of guinea pigs were compared with those of various bronchodilators. All test drugs abolished the resting tone of tracheal muscle completely. The potencies of test drugs which induced relaxation were in the order of: trimetoquinol greater than HOKU-81 greater than or equal to isoproterenol greater than salbutamol greater than terbutaline greater than or equal to tulobuterol greater than metaproterenol greater than clorprenaline. In acetylcholine-, histamine- or potassium-stimulated preparations, the intrinsic activities of 2-chlorophenyl derivatives were less than those of 3,4- or 3,5-dihydroxyphenyl derivatives and that of HOKU-81, 2-chloro-4-hydroxyphenyl derivative, lay between two groups. HOKU-81 showed weak positive chronotropic and inotropic actions and the potency ratio of HOKU-81 to isoproterenol was about 3/100 and less than 3/1000, respectively. Both chronotropic and inotropic actions of 2-chlorophenyl derivatives, including HOKU-81, were weak and the inotropic actions of drugs with N-t-butylamino radical were weaker than chronotropic actions. Effects of test drugs on trachea and atria were antagonized by propranolol 1 x 10(-6) or 1 x 10(-7) M. HOKU-81 appears to be a potent and selective beta 2-stimulant with a slight inotropic action.     

Cardiovascular effects of R- and S-enantiomers of Ro 22-9194, (2R)-2-amino-N- (2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate and (2S)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide L-tartrate, in dog heart preparations.

A newly synthesized compound, Ro 22-9194, relates in part of to the chemical structure of lidocaine. The cardiac effects of R- and S-enantiomers of Ro 22-9194 were investigated on isolated right atrial and left ventricular (LV) preparations which were cross-perfused with blood from another donor dog and an anesthetized open-chest dog. Each enantiomer (1-1,000 micrograms) decreased dose-dependently the sinus rate and atrial developed tension in the isolated right atrium (RA). The negative chronotropic responses to R- and S-enantiomers were not significantly different, and the negative inotropic responses to R- and S-enantiomers were also generally comparable. Both R- and S-enantiomers (10-3,000 micrograms) also decreased the ventricular developed tension in a dose-related manner similarly. In neurally decentralized, anesthetized, open-chest dogs, R- and S-enantiomers (0.1-3 mg/kg) injected into the femoral vein dose-dependently prolonged atrioventricular (A-V) conduction time and decreased heart rate (HR) and arterial blood pressure (ABP). Each enantiomer (3 mg/kg intravenously, i.v.) prolonged the interval between His bundle and ventricle rather than the interval between atrium and His bundle. There was no significant difference between R- and S-enantiomer-induced negative dromotropic actions. The duration of the negative dromotropic response to each enantiomer (3 mg/kg i.v.) was longer than that of the decrease in BP. These results suggest that the negative chronotropic, inotropic, and dromotropic effects of R- and S-enantiomers of Ro 22-9194 are not stereospecific in dog heart.     

Investigations into the cardiac effects of tolazoline in guinea pig atria and ventricular strips.

The positive inotropic, chronotropic and cyclic AMP producing effects of tolazoline were studied on atrial and ventricular preparations obtained from guinea pig heart. (1) The direct positive inotropic effects of tolazoline on the paced left atrial preparation from the guinea pig hearts was blocked by promethazine, but not by burimamide. Tolazoline did not elevate cyclic AMP levels in this preparation. (2) Tolazoline produced a positive chronotropic effect which was blocked by burimamide and not by promethazine and caused a 2-3 fold elevation of cyclic AMP in spontaneously beating right atria. (3) Burimamide antagonized the inotropic and cyclic AMP increasing effects of tolazoline on electrically driven ventricular strips. (4) The effects of tolazoline were unchanged by reserpine pretreatment of the guinea pigs or by prior exposure to phentolamine or propranolol. (5) These results suggest that tolazoline can activate both H1 and H2 receptors in the guinea pig heart. Furthermore the data suggests that H2 receptors are present in right atria and ventricle and that such receptors are associated with cyclic AMP. H1 receptors are present in the left atria and are not associated with the cyclic nucleotide.     

双白术内酯对豚鼠离体心房肌的作用

目的　以豚鼠离体心房肌为材料 ,研究新结构化合物双白术内酯对离体心房肌的作用。方法　采用豚鼠离体心房肌 ,测定给药前后心房的心率、心肌收缩力 ,左心房静息后增强作用及正性阶梯现象。结果　双白术内酯 (终浓度为1 19× 10 -5mol·L-1)能明显降低豚鼠离体右心房肌的收缩力 ,同时减慢其心率 ,此作用可完全被阿托品取消 ;双白术内酯使豚鼠离体左心房肌的正性阶梯作用降低 ,对左心房肌的静息后增强作用无影响。结论　双白术内酯对豚鼠离体心房肌有负性肌力和负性频率作用