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。     

一氧化氮介导血管紧张素(1-7)舒张豚鼠冠状动脉(英文)

研究血管紧张素 (1 7)对离体豚鼠心脏冠脉流量和心功能的影响 .采用Langendorff装置灌注离体心脏 ,记录冠脉流量 ,心率 ,左室内压及其最大变化速率 .结果显示血管紧张素 (1 7) (10 0 ,30 0nmol·L- 1)显著增加离体豚鼠心脏冠脉流量 ,但抑制心功能 .环氧化酶抑制剂吲哚美辛对血管紧张素(1 7)增加冠脉流量的作用无影响 ,而用一氧化氮合酶抑制剂L 硝基精氨酸甲酯处理后 ,血管紧张素(1 7)增加冠脉流量的作用被取消 .结果提示 :血管紧张素 (1 7)能舒张离体豚鼠心脏冠状动脉和损伤心功能 ,其舒张冠脉作用是由一氧化氮所介导     

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。     

内皮素-1对大鼠血管平滑肌的作用及川芎嗪的对抗效果

用离体大鼠的主动脉和培养的大鼠胸主动脉平滑肌细胞,研究了内皮素-1对主动脉的收缩作用及对主动脉平滑肌细胞增殖周期及能量代谢的影响,结果表明1.0～18.0nmol·L~1的内皮素-1能引起浓度依赖性血管收缩,川芎嗪能有效对抗内皮素-1血管收缩作用.100～100.0 pmol·L~1的内皮素-1能使S+G_2+M期细胞的比例增加,具有促进血管平滑肌细胞增殖的作用;10.0 pmol·L~1内皮素-1作用10 min可升高平滑肌细胞ATP含量,20 min之后ATP含量一直低于正常水平,内皮素1对平滑肌细胞ATP含量的影响呈双相作用,先升高后降低     

2-[(二乙胺)乙酰]-1,2,3,4-四氢-6,7-二甲氧基-1-[1′-(6″-甲氧-2″-萘)乙基]-异喹啉对离体豚鼠乳头状肌和心房的抑制作用(英文)

目的:研究2-[(二乙胺)乙酰]-1,2,3,4-四氢-6,7-二甲氧基-1-[1′-(6″-甲氧-2″-萘)乙基]-异喹啉(CPU57)对心脏的作用并与硝苯地平进行比较,着重于其作用机制的研究.方法:测量并记录以下参数:1)豚鼠右心房自发收缩的节律及张力;2)电刺激左心房和右室乳头状肌的等长收缩力.结果:CPU57象经典的钙拮抗剂硝苯地平一样,在0.01-100 μmol·L~(-1)浓度范围内对离体豚鼠心脏具有浓度依赖的负性频率和负性肌力作用,而前者明显弱于后者,且其对心脏的抑制作用比硝苯地平弱.将正常胞外Ca~(2 )浓度从1.5 mmol·L~(-1)降低至0.3或增高至7.5 mmol·L~(-1)可分别增强或减弱CPU57对电刺激左心房收缩的抑制作用.CPU57(1—10 μmol·L~(-1))还抑制CaCl_2所致电刺激左心房的量—效收缩曲线,pD_2′值为4.77.结论:CPU57对豚鼠心脏具有钙拮抗作用.     

粉防己碱对吗啡在离体豚鼠回肠中依赖性的作用(英文)

目的:研究粉防己碱(Tet)和尼莫地平(Nim)对吗啡在离体豚鼠回肠中戒断性反应的影响。方法:戒断性收缩由纳洛酮(1μmol·L~(-1))加入已在含吗啡(3μmol·L~(-1))的37.5℃ Krebs液中孵育4h的离体豚鼠回肠或加入从吗啡依赖豚鼠中取得的回肠引起。结果:离体豚鼠回肠在含吗啡的Krebs液中孵育4h,给Nim(0.01、0.05和0.1μmol·L~(-1))或Tet(1、10和50μmol·L~(-1))抑制其戒断性收缩。Nim和Tet体内或体外给药都能抑制吗啡依赖豚鼠离体回肠的戒断性收缩。结论:钙拮抗剂Nim和Tet抑制吗啡在离体豚鼠回肠的戒断性收缩。     

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     

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.     

胺碘酮对离体心肌的负性肌力作用

对离体左,右心房肌,胺碘酮(Ami)1～100μmol·L~(-1)均有负性肌力作用,30μmol·L~1明显抑制心肌静息后收缩,正阶梯和成对刺激效应,1～10μmol·L~1使苯福林,异丙肾上腺素,组胺和CaCl_2正性肌力作用的量效曲线呈非竞争性拮抗作用,心肌动作电位和收缩力同步记录发现,Ami 30μmol·L~1减弱心肌收缩,延长APD,但对平台期和V_(max)无影响.故Ami的负性肌力作用可能是抑制心肌细胞外Ca~(2+)内流和细胞内Ca~(2+)释放所致,并非选择性阻滞心肌α,β和H_2受体以及电压依赖性钙通道引起 .     

钩藤碱对离体豚鼠心脏电活动的影响

钩藤碱(Rhynchophylline,Rhy)具有降低血压、扩张血管、减慢心率和抑制心肌收缩力等作用;实验表明其松弛血管和子宫平滑肌的作用与钙拮抗有关.为了进一步探讨其对心脏的负性频率及负性肌力作用机制,本文报道Rhy对离体豚鼠灌流心脏电活动影响的初步观察.     

Vasodilator action of endothelin-1 in the perfused rat heart.

The effects of bolus injections of porcine endothelin (ET-1, 1-100 pmol) on the coronary microvasculature of isolated perfused rat heart were examined. Results show that ET-1 possesses dose-dependent vasodilator as well as vasoconstrictor properties. The vasodilator effect was transient and preceded its more pronounced and persistent vasoconstrictor action. ET-1-induced vasodilation in rat heart was not associated with release of prostacyclin (PGI2), as shown by radioimmunoassay (RIA) analysis of cardiac effluent and was not blocked by the cyclooxygenase inhibitors flurbiprofen (2 microM) or BW755c (7.5 microM). Neither was the dilatory response to ET-1 inhibited by haemoglobin (10 microM) or potentiated by superoxide dismutase (20 U/ml) but it was abolished by methylene blue (20 microM). However, methylene blue itself caused coronary dilation which could mask the vasodilator action of ET-1. These results show that in isolated perfused rat heart ET-1 possesses a vasodilator action that is not mediated by PGI2 and that may also be independent of release of endothelium-derived relaxing factor (EDRF).     

Blockade by burimamide of the effects of clonidine on cardiac contractility phosphorylase activation and cyclic adenosine monophosphate in isolated guinea pig heart

Clonidine in a dose-range of 2.5 microgram to 80 microgram caused positive inotropic effect, which was accompanied by increase in the cyclic AMP levels and phosphorylase-activation of the isolated perfused guinea pig heart. Clonidine-induced biochemical and mechanical effects were blocked by burimamide, an H2-receptor antagonist Propranolol (1 x 10(-6)M), phentolamine (1 x 10(-6)M) or reserpine pretreatment, did not affect the clonidine responses on the perfused guinea pig heart. Clonidine reduced the 4-methyl-histamine (H2-agonist) responses of guinea pig heart. Our data suggest that the cardiac effects of clonidine may be due to stimulation of H2-type of receptors.     

沙棘总黄酮对离体心脏的抗心律失常作用

沙棘总黄酮(TFH)对离体大鼠心脏可显著延长缺氧性心律失常出现时间,提高室颤阈值,延缓房室传导,减慢心率,减弱心肌收缩力和对抗由缺氧引起的心率减慢及心肌收缩力减弱的作用。TFH可轻度延长离体豚鼠左房功能不应期,明显对抗乌头碱诱发离体豚鼠右房节律失常的作用。     

Effects of formaldehyde on cardiac function

This investigation examined the effect of formaldehyde (HCHO) on cardiac function in in vitro cardiac preparations and in situ hearts of guinea pigs and rabbits. Though HCHO (0.2-4 mg/kg, i.v.) produced noticeable bradycardiac and negative inotropic responses in anesthetized guinea pigs and rabbits, the responses to HCHO were far less in isolated guinea pig auricles and perfused hearts (Langendorff's preparations). The inhibitory responses to HCHO in the isolated auricles and perfused hearts were obtained at concentrations 200-400 times and 4-8 times higher than the blood concentrations attained in anesthetized animals, respectively. The responses in the isolated preparations were not significantly affected by propranolol. The bradycardiac response to the intravenously administered HCHO in anesthetized animals was not significantly affected by atropine or vagotomy, but was markedly attenuated by propranolol, reserpine or surgical denervation of the heart. These results indicate that the direct action of HCHO on the heart plays only a small role in the negative chronotropic response to HCHO in anesthetized animals. Furthermore, the negative chronotropic effect of HCHO in animals seems to be caused mainly by the inhibition of sympathetic nervous activity through the central nervous system.     

Combined blockade of endothelin-1 and thromboxane A(2) receptors against postischaemic contractile dysfunction in rat hearts

1. Endothelin-1 (ET-1) may play a role in myocardial ischaemia/reperfusion injury because both the release and vasoconstrictor effect of ET-1 are increased after ischaemia. Since the increased vasoconstrictor effect of ET-1 can be mediated by ET-1-induced release of thromboxane A(2) (TXA(2)), the aim of this study was to test whether combined blockade of ET and TXA(2) receptors protects the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion. 2. Bosentan (antagonist for ET(A) and ET(B) receptors, 1 microM based on concentration-response curves of ET-1), SQ 30,741 (antagonist of TXA(2) receptors, 0.1 microM), or the combination thereof was administered to isolated perfused rat hearts undergoing 15 min of global ischaemia and 60 min of reperfusion. 3. Neither bosentan or SQ 30,741 alone, nor the combination thereof, improved the incomplete postischaemic recovery of coronary flow, left ventricular developed pressure, phosphocreatine, or ATP. However, they attenuated ischaemia-induced acidosis but this did not translate into a measurable effect on haemodynamic or metabolic variables. 4. Thus, combined blockade of ET and TXA(2) receptors does not protect the coronary flow, contractile performance, and cardiac energy metabolism during ischaemia and reperfusion in isolated perfused rat hearts. This finding suggests that neither ET-1 nor ET-1-induced release of TXA(2) play a major role in the postischaemic recovery of the cardiac contractile function and energy metabolism.     

Pharmacological studies on 3-[gamma-(p-fluorobenzoyl)propyl]-2,3,4,4a,5,6-hexahydro-1 (H)-pyrazino(1,2-a) quinoline hydrochloride (compound 69/183). Part II: Effect on cardiac dynamics

Effect of 3-[gamma-(p-fluorobenzoyl)propyl]-2,3,4,4a,5,6-hexahydro-1-(H)-pyrazino(1,2-a)quinoline hydrochloride (centpyraquin, 69/183) on the cardiac function has been studied in situ in cat and dog and on isolated guinea pig heart. Centpyraquin (1.0 mg/kg i.v.) decreased cardiac output (20%) and total peripheral resistance (18%) along with blood pressure (40%). The decrease in dp/dt and PTI were secondary to hypotension. The contractility of the auricle as well as the ventricle was not decreased. In the heart-lung preparation of dog, centpyraquin (5 mg) had an inhibitory effect on the heart. The contractility of the isolated guinea pig heart was not changed up to 200 micrograms dose but higher doses had negative inotropic effect. The compound had no significant effect on ECG of cat. The effect of norepinephrine on dp/dt and PTI was potentiated. Isoproterenol induced hypotension was not changed but the cardiac effects were potentiated.     

Effect of removing the endothelium on the vascular responses induced by leukotrienes C4 and D4 in guinea-pig isolated heart.

The coronary vascular endothelium of the guinea-pig isolated perfused heart was removed by treatment with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS), a zwitterionic detergent. After CHAPS treatment of the heart the vasoconstrictor responses of leukotriene (LT) C4, LTD4 and angiotensin II (AII) were significantly attenuated whereas the vascular actions of U46619, a thromboxane (Tx) A2 mimetic, and endothelin-1 (ET-1) were unaltered. The endothelium-dependent vasoconstrictor response of LTC4 and LTD4 could not be attributed to the release of TxA2, platelet-activating factor or AII since indomethacin, WEB 2086 and captopril had no effect on LT actions. However, in the presence of cromakalim, a potassium channel activator, the vasoconstrictor effects induced by LTC4, LTD4 and AII were significantly attenuated to a greater extent than the responses of U46619 and ET-1. The results suggest that in the coronary vasculature of the guinea-pig isolated heart the vasoconstrictor responses of LTC4, LTD4 and AII are endothelium-dependent and may involve a cromakalim-sensitive mechanism.     

Endothelin-1 has a dilator effect on neonatal pig pulmonary vasculature.

Endothelin-1 (ET-1), a 21-residue potent vasoconstrictor peptide produced by endothelial cells, was reported to cause vasodilation in the systemic and pulmonary vascular beds. Therefore, in isolated perfused lungs from 7-day-old piglets, we studied the effects and the mechanisms responsible for the dilator effect of ET-1. ET-1 produced a mild transient decrease in perfusion pressure at low doses (less than 10(-7) M/g dry lung); at higher doses, a potent long-lasting vasoconstriction was noted. Indeed, the constrictor effect of ET-1 was at least equal to or greater than that of U-44069 and prostaglandin D2 (PGD2). When the vascular tone of the preparation was increased with U-46619, another stable endoperoxide analogue, the dilator response to low doses of ET-1 was increased, while the constrictor response remained unchanged. Indomethacin (2.8 x 10(-6) M) and glybenclamide (an ATP-sensitive potassium channel inhibitor) (10(-5) M) did not alter the responses to ET-1. The endothelium-derived relaxing factor (EDRF) inhibitor Nw-nitro-L-arginine (2 x 10(-4) M) not only inhibited the dilator response to ET-1 almost completely, but also potentiated the constrictor response. Finally, Nw-nitro-L-arginine alone had a mild vasoconstrictor effect in newborn pig lung. The results of these studies indicate that ET-1 has both vasodilator and vasoconstrictor activity in neonatal pig pulmonary vascular bed. This vasodilator activity may be mediated by EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of age-related differences in the cardiotoxic action of digitalis

Age-associated ouabain sensitivity was investigated in isolated perfused guinea pig heart and the findings were correlated with its receptor function. Ouabain (0.1 mumol L-1) produced average positive inotropic responses of 22% in 15-day-old, 25% in 4-6 month-old, and 34% in 18-24-month-old guinea pig hearts. The time required to produce the greatest positive inotropic response was 28 min in 15-day- to 6-month-old guinea pig hearts and 20 min in 18-24-month-old guinea pig hearts. To cause arrhythmias and cardiac arrest, 2.1 mumol L-1 ouabain was required in age groups of 15 days to 6 months, and 1.2 mumol L-1 in age groups of 12-24 months. The time of onset of arrhythmias and cardiac arrest was also significantly less in older than in younger animals. Cardiac membranes from 12-24-month-old guinea pig hearts had significantly lower Na+, K+ -ATPase activity per mg of sarcolemmal protein and numbers of [3H]ouabain binding sites than those from 28-day- to 6-month-old hearts. The enzyme inhibition by 0.1 mumol L-1 ouabain was, however, less in younger than in older groups. The difference in the inhibition of enzyme was reflected in lower ouabain binding affinity (Kd) in younger animals. The data confirm the existence of an age-related difference in ouabain sensitivity and suggest that these differences may be due to changes in receptor function.     

Effect of etorphine on adrenergic neurotransmission in the rat and guinea pig heart

The effect of etorphine (ET) on nerve stimulation-mediated release of norepinephrine (NE) was investigated in isolated rat and guinea pig hearts. Hearts were perfused with Krebs bicarbonate solution via the aorta and the overflow of NE was measured after stimulation of the heart. ET (0.001-0.1 mumol/l) caused a dose-dependent inhibition of NE release in both preparations. Inhibition of NE release from guinea pig hearts ranged from 13% at 0.001 mumol/l to 24% at 0.1 mumol/l. The same concentrations of ET decreased NE release by 10 and 36% in the rat heart. The inhibitory effect of ET was blocked by naloxone. It is concluded that presynaptic opioid receptors located on the adrenergic neuronal terminals may be involved in the regulation of adrenergic neurotransmission in the rat and guinea pig heart.