L-四氢巴马汀对离体豚鼠心房的作用

THP和Ver均能对抗CaCl_2所致离体豚鼠右房正性频率作用,非竞争性拮抗CaCl_2左房正性肌力作用以及Iso右房正性频率和左房正性肌力作用。THP和Ver浓度依赖性和频率依赖性地抑制左房收缩中的阶梯现象,使正阶梯翻转为负阶梯。而对休息后加强影响较小。结果提示THP对心房的抑制作用与Ver相似,与拮抗Ca~(2+)有关,可能主要通过抑制心肌细胞外Ca~(2+)内流所致。     

左旋四氢巴马汀对几种激动剂所致气管收缩作用的影响

在离体豚鼠气管螺旋条L—THP抗BaCl_2,KCl,5-HT,His,Ach所致收缩作用与Ver及Pap均不同。L-THP抗BaCl_2,KCl,5-HT,His次最大反应量所致收缩的IC_(50)值分别为3.5×10~(-5)mol/L,4.5×10~(-5)mol/L,2.5×10~(-5)mol/L,8.9×10~(-5)mol/L。各激动剂对L—THP的敏感性与其对胞外钙的相对依赖性顺序相一致。但L-THP抗KCl及5-HT的作用强度无显著差异,提示L-THP能阻断钙内流并具相似强度的抗5-HT作用。     

雌酚酮衍生物EA204对离体兔血管平滑肌的舒张作用

目的探讨雌酚酮衍生物(EA204)对离体兔血管平滑肌的作用及其机制。方法以离体兔主动脉条为标本,观察了EA204对去甲肾上腺素(NE)、氯化钾(KCl)引起的兔主动脉条收缩的影响;对氯化钙(CaCl2)累积收缩量效曲线的影响,并与维拉帕米(Ver)相比较。通过对比格列苯脲(10μmol.L-1)孵育前后EA204对BaCl2、KCl的舒张量效曲线,研究EA204对钾通道的作用。结果EA204(10~3 mmol.L-1)可以剂量依赖性地抑制NE、KCl收缩的兔主动脉条;EA204(10μmol.L-1)或Ver(0.1μmol.L-1)都使CaCl2累积收缩量效曲线呈剂量依赖性右移,但EA204孵育后CaCl2量效曲线最大反应基本不变,而Ver使最大反应降低;加入格列苯脲(10μmol.L-1)孵育后EA204对BaCl2、KCl收缩的主动脉条的舒张量效曲线发生明显变化,EA204的舒张作用被抑制。结论EA204具有舒张离体兔血管平滑肌的作用,其作用机制与其钙通道阻断作用和钾通道开放作用有关。     

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。     

阿司匹林铜对离体兔主动脉血管条收缩的影响(英文)

目的:观察阿司匹林铜对离体免胸主动脉血管平滑肌的作用。方法:取免胸主动脉条,观察阿司匹林铜对去甲肾上腺素(NE)、KCl、CaCl_2诱导收缩作用的影响。结果:证实阿司匹林铜和对照物硫酸铜拮抗NE诱导的兔胸主动脉条收缩,IC_(50)分别为31nmol/L和0.29μmol/L,而阿司匹林本身没有拮抗作用。阿司匹林铜对KCl、CaCl_2诱导的收缩没有影响。在去内皮细胞兔胸主动脉条上,观察到相同的作用。结论:阿司匹林铜具有较强的拮抗NE诱导离体兔胸主动脉条收缩的作用,但不能拮抗KCl、CaCl_2诱导的收缩,提示阿司匹林铜通过阻断受体调控钙通道,舒张血管平滑肌。     

蛇床子素对豚鼠离体回肠和结肠带的作用

以豚鼠离体回肠和结肠带为标本,观察蛇床子素(Ost)的作用与Ca~(2+)的关系。结果表明:Ost和钙拮抗剂Ver产生剂量依赖性抑制乙酰胆碱(ACh)、组胺及KCl所致回肠条或结肠带的收缩;非竞争性拮抗CaCl_2累积量—效曲线,pD_2分别为4.41±0.15,7.0±0.2。Ost 100μmol/L和Ver 1μmol/L均能对抗小剂量Ca~(2+)所致结肠带收缩,但被加入较大量Ca~(2+)所取消。Ost和Ver均能抑制ACh诱导的依内钙性收缩,不影响依外钙性收缩。结果提示Ost具有钙拮抗作用,其作用方式与Ver类似。     

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。     

蛇床子素对豚鼠离体回肠和结肠带的作用

以豚鼠离体回肠和结肠带为标本,观察蛇床子素(Ost)的作用与Ca²⁺)的关系。结果表明:Ost和钙拮抗剂Ver产生剂量依赖性抑制乙酰胆碱(ACh)、组胺及KCl所致回肠条或结肠带的收缩;非竞争性拮抗CaCl₂累积量—效曲线,pD₂分别为4.41±0.15,7.0±0.2。Ost 100μmol/L和Ver 1μmol/L均能对抗小剂量Ca²⁺所致结肠带收缩,但被加入较大量Ca²⁺所取消。Ost和Ver均能抑制ACh诱导的依内钙性收缩,不影响依外钙性收缩。结果提示Ost具有钙拮抗作用,其作用方式与Ver类似。     

薤白提取物对兔离体主动脉条的作用

本实验以离体兔主动脉条为标本 ,对薤白 (EA)的扩血管机制进行了探讨 .观察了薤白对去甲肾上腺素 (NE)、氯化钾 (KCl)和氯化钙 (CaCl2 )的剂量 效应曲线的影响及主动脉条的α受体及 β受体的作用 .观察了EA对NE引起的兔主动脉条两种收缩成分的影响 .结果表明EA能舒张已为氯化钙、高钾和去甲肾上腺素收缩的兔主动脉条 ,使NE、KCl、CaCl2 的剂量 效应曲线非平行右移 ,最大效应降低 .EA松弛血管平滑肌的作用不依赖于阻断α受体或 β受体 ,而与戊脉安 (Ver)相似 ,是通过阻断钙通道实现的 .但它们阻断钙通道的方式不同 .EA可能无选择性阻断电位依赖性钙通道和受体操纵性钙通道 .因此EA的扩血管机制与其对钙通道阻断作用有关 .     

地奥心血康对大鼠主动脉~（45）Ca内流的影响

用~（４５）Ｃａ跨膜流动测定方法研究地奥心血康及维拉帕米对大鼠主动脉Ｃａ~（２＋）跨膜内流的影响。结果：地奥心血康５－５００μｇ／ｍＬ和维拉帕米０．０１１－１．１μｍｏｌ／Ｌ，不影响静息~（４５）Ｃａ的内流，但均能浓度依赖性抑制去甲肾上腺素１．２ｍｏｌ／Ｌ和ＫＣｌ１００ｍｍｏｌ／Ｌ引起的~（４５）Ｃａ内流。说明地奥心血康能阻滞细胞外Ｃａ~（２＋）通过受体操纵与电压依赖钙离子通道的内流。     

Gender-Specific Inhibition of Ca2+ Entry Mechanisms of Arterial Vasoconstriction by Sex Hormones

1. The clinical observation that hypertension is more common in males and postmenopausal women than in premenopausal women suggests vascular protective effects of female sex hormones, including hormone-mediated inhibition of vascular tone. The purpose of the present study was to investigate whether the Ca2+ mobilization mechanisms of vascular smooth muscle contraction are modified by gender and sex hormones. 2. Active stress and [45Ca2+] influx were measured in de-endothelialized aortic strips isolated from intact and gonadectomized male and female Sprague-Dawley rats. In normal Krebs' (2.5 mmol/L Ca2+), both phenylephrine (Phe; 10(-5) mol/L) and membrane depolarization by 96 mmol/L KCl increased active stress to 15.5 +/- 1.3 x 10(3) and 14.8 +/- 1.2 x 10(3) N/m2, respectively, and Ca2+ influx to 28.4 +/- 1.4 and 32.3 +/- 1.5 mumol/kg per min, respectively, in intact males. The Phe- and KCl-induced stress and Ca2+ influx were significantly reduced in intact females. Gonadectomy was associated with no significant changes in the Phe- and KCl-induced stress and Ca2+ influx in males, but was associated with significant enhancement in females. In Ca(2+)-free (2 mmol/L EGTA) Krebs', stimulation of intracellular Ca2+ release by Phe or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rats. 3. Exogenous application of 17 beta-oestradiol, progesterone or testosterone to aortic strips caused concentration-dependent inhibition of Phe- and KCl-stimulated contractions and Ca2+ influx. 17 beta-Oestradiol was the most effective hormone and its relative potency was intact males, castrated males and ovariectomized females > intact females. 4. Thus, vascular reactivity and Ca2+ entry in aortic smooth muscle are reduced in the presence and enhanced in the absence of female gonads. Both male and female sex hormones cause vascular relaxation, mainly by inhibiting Ca2+ entry, with oestrogen being the most effective, particularly in the absence of female gonads. The results suggest that a cellular mechanism of oestrogen-induced vascular relaxation involving inhibition of Ca2+ entry into vascular smooth muscle is gender dependent.     

八肽胆囊收缩素对抗吗啡抑制大鼠脑突触小体钙摄取的作用

用大鼠脑的膜制备观察吗啡和CCK-8对突触小体摄取~(45)Ca~(2+)的影响。吗啡(10 nmol/L～1μmo1/L)抑制突触小体对~(45)Ca的摄取,该作用能被1μmol/L纳洛酮完全阻断。CCK-8(10nmol/L～1μmol/L)本身能抑制突触小体~(45)Ca摄取,但它在10nmol/L和100 nmol/L时能对抗吗啡对~(45)Ca摄取的抑制作用,浓度提高到1μmol则不能对抗吗啡的这一作用。CCK-8抑制突触小体摄取~(45)Ca,以及对抗吗啡的~(45)Ca摄取抑制的作用,皆能被CCK受体拮抗剂丙谷酰胺(2μmol/L)所阻断.捉示CCK-8是通过激动CCK受体而拮抗吗啡抑制~(45)Ca摄取的,CCK-8的这一拮抗作用可能是其抗阿片作用的机理之一.     

莲心碱对几种平滑肌作用的研究

莲心碱（Ｌｉｅ）抑制去氧肾上腺素（ＰＥ），５－羟色胺（５－ＨＴ），组胺（Ｈｉｓ）和高Ｋ＋引起的兔主动脉环收缩，对ＰＥ引起的收缩，其抑制作用更为明显；也抑制ＰＥ所致兔尿道平滑肌的收缩。在兔主动脉环和大鼠肛尾肌标本，Ｌｉｅ使甲氧胺（Ｍｅｔ）及ＰＥ的量效曲线平行右移，最大反应不压低，ＰＡ２值分别为６．８和６．６。Ｌｉｅ还明显抑制去甲肾上腺素（ＮＥ）所致的内钙释放，而对ＮＥ所致外钙内流影响较小。提示：Ｌｉｅ具有阻断肾上腺素α１受体和抑制细胞内钙释放作用。     

Effects of cadralazine on contractions induced by Ca2+ and norepinephrine in isolated rabbit aortic strips

Antagonistic effects of the new antihypertensive agent cadralazine (ethyl(+/-)-6-[ethyl(2-hydroxypropyl)-amino]-3-pyridazinecarbazate ) and its metabolite ISF-2405 [+/-)-6-[ethyl(2-hydroxypropyl)amino]-3-hydrazinopyridazine) on contractile responses to CaCl2 in K+-depolarised medium and to norepinephrine (NE) in Ca2+-free medium were compared with those of hydralazine using isolated rabbit abdominal aortic strips. Even at high doses of cadralazine (10(-4) mol/l), ISF-2405 (10(-5) mol/l) and hydralazine (10(-5) mol/l), only less than 10% inhibition was observed on dose-dependent contractions induced by CaCl2, 0.05 to 6.4 mmol/l, in K+ 40 mmol/l medium. NE produced dose-dependent contractions even in Ca2+-free medium at concentrations of 10(-9) to 3 X 10(-5) mol/l, and the maximal response was diminished to about 45% of the response in the presence of Ca2+. Cadralazine 10(-4) mol/l exerted no effect on Ca2+-free NE-induced contractions, while ISF-2405 and hydralazine at concentrations of 10(-7) to 10(-5) mol/l were equipotent, showing marked dose-dependent, non-competitive inhibition on NE-induced contractions. These results suggest that ISF-2405 and hydralazine show vasodilating effect through the inhibition of the Ca2+-release from intracellular storage but not via inhibition of the potential dependent Ca2+ influx.     

汉防己甲素对气管平滑肌45Ca内流的影响

本文应用国产⁴⁵CaCl₂研究汉防已甲素(以下简称为汉甲)对气管平滑肌钙内流的影响。汉甲对犬与豚鼠气管平滑肌基础的⁴⁵Ca内流量无明显的影响;60μg/ml汉甲对犬气管平滑肌组胺兴奋与高钾打开电位操纵通道(POC)的5 min⁴⁵Ca内流量的抑制率,分别为11.1%与38.3%;60μg/ml汉甲对豚鼠气管平滑肌组胺与高钾兴奋的5min⁴⁵Ca内流量的抑制率分别为48.7%与33.3%,10μg/ml或20μg/ml汉甲虽对犬或豚鼠气管平滑肌组胺兴奋的、高钾兴奋和/或打开POC的⁴⁵Ca内流量具有一定的抑制作用,但无统计学意义。说明汉甲对气管平滑肌POC与受体操纵通道(ROC)均有阻断作用,由于对高钾兴奋和/或打开POC的⁴⁵Ca内流阻断是完全的,而对组胺兴奋和打开RCC的⁴⁵Ca内流阻断是部分的,提示汉甲优先阻断气管平滑肌的POC,60μg/ml汉甲对气管平滑肌POC的阻断强度与50μg/ml异搏定相当。汉甲的钙通道阻断作用可能与其拮抗过敏介质收缩气管的作用有关。     

钩藤碱对大鼠离体子宫收缩反应的影响

本文观察到Rhy对催产素和高K~+去极化后Ca~(2+)引起的大鼠离体子宫收缩均有抑制作用,前一作用可被Ca~(2+)所对抗。CaCl_2量效曲线显示,Rhy对其呈非竞争性拮抗。在无Ca~(2+)高K~+液中,Rhy10μM抑制催产素依赖细胞内Ca~(2+)引起的收缩,而Rhy 40μM除加强这一作用外,对催产素依赖细胞外Ca~(2+)的收缩亦有抑制作用。     

Effects of l-tetrahydropalmatine on isolated rabbit arterial strips

The effects of l-tetrahydropalmatine (THP) on isolated rabbit aortic, renal and superior mesenteric arterial strips were studied in comparison with verapamil (Ver). THP and Ver shifted the KCl, CaCl2, norepinephrine (NE) and 15-methyl prostaglandin F2 alpha dose-response curves to the right in a non-parallel fashion, and decreased the maximal response, showing noncompetitive antagonism. THP was less potent in dilating arterial strips than Ver. THP and Ver obviously inhibited the intracellular Ca2+-dependent component of NE-induced contraction of the aorta, but only slightly decreased the extracellular Ca2+-dependent component when the concentration of THP or Ver was very high (THP 0.1 mmol/L, Ver 10 mumol/L). The results suggest that THP, similar to Ver, mainly inhibits potential-operated calcium channels. THP and Ver were more potent in dilating renal and superior mesenteric arterial strips than aortic strips. The results indicate that the vasodilation effect of THP is similar to that of Ver and that THP probably has a calcium antagonistic effect.     

Calcium antagonistic properties of nicardipine, a dihydropyridine derivative assessed in isolated cerebral arteries and cardiac muscle

Calcium antagonistic properties of nicardipine (YC-93), a 1,4-dihydropyridine derivative, were studied in isolated cerebral artery and cardiac tissues of rabbits and dogs. Calcium antagonism was assessed in electrically stimulated rabbit basilar artery. Nicardipine at 10(-7) mol/l shifted to the right the dose-response curve for Ca of the phasic contraction evoked by electrical stimulation with an alternating current, and at higher concentration it reduced the maximum tension and slope of the dose-response curve. Nicardipine inhibited the augmented contraction produced by high K, k-strophanthin and 5-hydroxytryptamine. It also caused dose-dependent inhibition of 45Ca uptake enhanced by 80 mmol/l K in dog basilar artery, and had a slight effect on the resting 45Ca uptake. In rabbit basilar artery treated with saponin, nicardipine in a dose of 10(-5) mol/l had no apparent effect on the increase in tension induced by excess Ca. Nicardipine had negative inotropic and chronotropic actions. These results suggest that nicardipine, like nifedipine, has a relative high vascular selectivity, and primarily acts by inhibiting Ca influx through the plasma membrane of vascular and cardiac tissues.