碘化二甲基木防己碱对清醒及急性肾型高血压大鼠的降压作用

前文报道,iv碘化二甲基木防己碱(DTI)对麻醉狗、猫、兔及大鼠均有降压作用,其降压作用可能与阻断交感神经节的作用有关。本文研究了DTI长期po对清醒和麻醉大鼠的降压作用及iv对急性肾型高血压大鼠血压的影响。     

碘化二甲基木防己碱对清醒及急性肾型高血压大鼠的降压作用

In acute renal hypertensive rats, the blood pressure could be reduced from 148.8±7.9 mmHg to 123.6±9.3 mmHg by intravenous injection of dimethyl trilobine iodide (DTI) at the dosage of 0.5 mg/kg. The hypotensive effect persisted more than 40 minutes.DTI also lowered the blood pressure of unanesthetized rats by feeding 3～10 mg/kg daily for 28 days, but it did not affect the SGPT of rats.     

槐果碱的降压作用及其机制

静注槐果碱(SC)1,5,10,15mg/kg分别降低麻醉犬动脉血压7.1±0.8%,13.2±1.4%,21.0±3.9%,25.9±6.4%。降压时间持续30min左右.SC灌胃给药亦能降低肾性高血压大鼠血压值。SC15mg/次能使因连续电刺激而强直收缩的瞬膜标本松弛。用导纳图仪测定整体犬血流动力学发现iv SC 25mg/kg提高 dy/dt_(max)18%,HI40%,缩短Q-Y间期37%,而对SI,CI,CO等泵功能指标无影响。股动脉内注射SC50,100,200μg/kg使犬后肢血管阻力分别下降13.1±1.6%,20.5±4.6%,27.8±4.1％。说明其降压作用与扩张外周血管和交感神经节阻滞有关。     

尼群的平、间硝苯吡啶及其油剂降压特点的研究

用肾动脉狭窄观察大鼠形成高血压过程,血压稳步上升,到40～47天达稳定状态。尼群的平降压峰值为4～6h,高血压动物长期给药(一个月)后24h仍使血压降低原水平16％。尼群的平降压作用较间硝苯吡啶弱,前者降低原水平33.4％,后者39.1％,二者比较F值为9.79,P<0.01。二者用油剂20mg/kg im,隔天或三天给药一次,降压作用显著持久,均可持续48～72h之久。     

异钩藤碱的降压及血流动力学作用(英文)

在清醒正常血压大鼠,iv Isorhy2.5 mg/kg对BP及HR均无明显影响,iv5 mg/kg则使DAP和HR降低,但SAP无变化,剂量加大至10 mg/kg时,上述各项指标均明显降低。经十二指肠内给Isorhy10 mg/kg后20 min出现BP及HR降低,而20mg/kg剂量组于10 min开始出现BP及HR的进一步下降.Isorhy(10mg/kg和2 mg/kg,iv)亦能分别降低肾性高血压清醒大鼠和麻醉犬的BP。icv表明中枢不是降压作用的主要部位,在体条件下无α-受体和神经节阻断作用。Isorhy使清醒大鼠和麻醉犬的LVSP,dP/dt_(max),V_(max)等左室收缩性能指标短暂下降,而BP呈持久性降低。在麻醉犬给药后CO,CI,HR及LVWI下降的同时SV和SI不变,TPVR降低,反映心肌氧耗的TTI明显减少.结果提示Isorhy具有肯定的降压作用,其持续降压与扩张血管及减慢心率导致CO下降有关,而其负性肌力作用亦可能参与了早期的降压机理.Isorhy能减少心肌氧耗对高血压心肌劳损可能有保护意义。     

莲心碱对大鼠血流动力学及兔心房特性的影响

iv莲心碱(Lien)3mg/kg可一过性地抑制麻醉或毁脊髓大鼠血流动力学诸指标,对麻醉大鼠LVP,+dp/dt_max及SAP的抑制较奎尼丁(Qui)3mg/kg为强;Lien 1～30 mg/kg可依量性地产生上述效应,12mg/kg的Lien和Qui分别使LVP,+dp/dt_max,SAP下降33%,37%,29%和9%,12%,9%,而二者对其它血流动力学参数的抑制程度却相近。Lien 12 mg/kg对血流动力学诸指标的抑制强度与维拉帕米(Ver)1 mg/kg相似。Lien 1～100μmol/L可浓度依赖性地抑制左房收缩力和右房频率。提示其对血流动力学影响的特性与Ver更相似而与Qui有别。     

小唐松草碱的降压作用

小唐松草碱(ocoteine)1～10 mg/kg iv对麻醉、清醒的正常血压大鼠和肾性高血压大鼠均有迅速而持久的降压作用,脑室内注射给药也有明显的降压作用。切断双侧迷走神经合用阿托品,及用苯海拉明不影响 ocoteine的降压作用。在毁脊髓大鼠,ocoteinc 1～3mg/kg使甲氧明的量效曲线平行右移,而不影响B-HT920的量效曲线。结果提示ocoteine选择性阻断血管性平滑肌突触后α_1受体,并可能具有中枢性降压作用;其降压作用不是通过迷走神经或释放组胺。     

水杨酸双异丙胺降压作用的药理研究

静脉或十二指肠注射水杨酸双异丙胺对麻醉大鼠和狗均有快速显著的降压作用。给清醒的肾性高血压狗以50～100mg/kg灌胃亦有降压效果,一般持续1.5～5小时。其降压作用主要为总外周血管阻力的降低,而对心肌收缩性无明显抑制。动脉内注射也不直接扩张血管。推动脉与静脉注射1mg/kg的降压效果以及对血流动力学的作用相似。提示主要不是中枢性降压。2～5mg/kg静注能阴滞烟碱的心血管作用。说明隆压可能与阴滞神经节有关。     

间硝苯啶、硝苯啶与尼群的平对动物降压作用的比较性研究

在清醒正常血压大鼠、免以及肾型高血压大鼠,比较了m-nif、nif及nitr的降压强度,和降压的时间动态过程,三药的降压作用与对照组及自身前后对比,统计学上均非常显著。m-nif与nitr降压持续时间较nif长。从清醒正常血压大鼠降压的量效关系比较,m-nif、nif和nitr的ED₅₀)分别为33.7±3.4,45.6±3.6和51.2±4.1 mg/kg(即90±9,132±10,142±11μmol/kg)。按克分子量计算对比m-nif的降压强度最大,nitr最弱。但三药对正常血压及肾型高血压动物的降压作用,按组间对比,无统计学差异。     

碘化二甲基木防己碱对实验性心律失常及心肌电活动的作用

静脉注射碘化二甲基木防己碱(DMT)1mg/kg,有对抗乌头碱诱发大鼠心律失常的作用。腹腔注射DMT0.25mg/kg,有对抗氯仿-肾上腺素诱发家兔心律失常的作用。腹腔注射DMT1.5mg/kg,对抗哇巴因诱发豚鼠心律失常,使豚鼠心室肌细胞动作电位平台期延长。DMT3.0×10^-6使家兔离体心房肌功能不应期延长。     

羊踯躅降压成分的研究

从羊踯躅的花中提取分离的4个单体,Rdl是其中之一。给小白鼠静脉注射Rdl的LD_(50)为4742μg/kg。给猫静脉分别注射Rdl 100,300和500μg/kg,平均血压分别下降10.9％(P<0.01)、23.8％和39.3％,其中500μg/kg,降压维持时间(±SD)71.3±15.5min。兔静脉注射5～100μg/kg,血压下降3.2～29.9％,作用维持26.6～101.7min。大白鼠静脉注射100～700μg/kg,血压下降16.2～51.7％,作用维持11.7～100min。RdI的降压作用可能是非中枢性的,与交感神经系统无关,与胆碱能神经系统有关。     

治疗高血压药物的研究 ⅩⅢ.野菊花成分HC-1的实验治疗及毒性

野菊花降压有效。本文实验用热醇提取出有效成分HC-1,并研究其疗效及毒性。麻醉猫小肠注射50—100毫克/公斤,2小时内的降压面积百分比为-19至-22%。正常血压狗4只,分别灌服50,100,130及150毫克/公斤,舒张压分别下降0,24,8及36毫米汞柱,作用缓慢,维持2小时以上。慢性肾型高血压狗3只,前2周每日灌胃100毫克/公斤,第3周每日灌胃200毫克/公斤。其中2狗血压显著降低。这3狗每周作心电图、血清磺溴酞钠存留率及全血非蛋白氮含量的测定,未见到严重毒性反应。另1只正常狗每日服300毫克/公斤,连续3周,除有时呕吐外,亦无其他严重毒性反应。HC-1产量较高,毒性不大,作用缓和,对麻醉与不麻醉动物有一定降压效果,可以推荐临床试用。     

云南萝芙木的药理研究,—云南萝芙木的降压作用及其机制

自从夹竹桃科植物印度蛇木(Rauwolfia Serpentina Benth.)的各种制剂(特别是Reserpine)对高血压的疗效引起全世界医、药学家的重视后,我国学者也从本国寻找其代替品,并在云南、广东、广西及海南岛找到了同属植物蘿芙木R. Verticillata (Lour.) Baill.李承祜等及云南药用植物研究所曾做过其生药学的研究。赵承嘏等曾从广东蘿芙木提出一种生物硷,名为蘿芙甲素(Rauwolfia A),经夏炳南等,林吉强等进行了药理研     

汉防己甲素及乙素对心血管系统的作用

1.以汉防已甲素或乙素3毫克/公斤靜脉注射、肌肉注射或灌胃,均可使麻醉猫的血压明显下降,甲素之降压作用較乙素大而持久,甲素靜脉注射时,降压作用急驟而持久,可維持1—5小时;肌肉注射及灌胃时,降压作用較緩慢,但亦甚持久。2.乙素之降压作用較甲素弱而短暫,靜脉給药之作用較肌肉注射为强,灌胃之降压作用又較肌肉注射为弱。3.静脉注射甲素或乙素3毫克/公斤,在血压下降的同时,可見暫时性心收縮力減弱;但肌肉注射同样或更大剂量(5毫克/公斤),則不出現心力抑制現象,甲素对心率之影响較少,乙素則往往引起心率減慢,心动电流圖上仅見R波幅度之減小,对P-R間歇及T波等均無影响。4.甲素及乙素可使脾容积增加,但在血压急剧下降时,則可使脾容积縮小。5.甲素及乙素均可使离体兎耳血管扩張,直接对平滑肌之抑制作用及神經反射机制均参加在內.甲素之血管扩張作用較乙素及罂粟硷为大而持久。     

Antihypertensive effect of CV-4093.2HCl, a new calcium antagonist, in three rat models of hypertension

The hypotensive action of CV-4093.2HCl (CV-4093), a new calcium antagonist, was studied in spontaneously hypertensive, renal hypertensive, DOCA-salt hypertensive and normotensive rats. CV-4093 (3 and 10 mg/kg, p.o.) dose-dependently decreased systolic blood pressure in the three types of hypertensive rats. At the dose of 10 mg/kg, the compound decreased the blood pressure to the normotensive level between 1 and 3 hr after it was administered; the antihypertensive effect lasted for at least 8 hr. The systolic blood pressure in normotensive rats was also decreased at 3 and 10 mg/kg, p.o., but less evidently than in the hypertensive rats. When the antihypertensive effect of CV-4093 was compared with that of seven known calcium antagonists in spontaneously hypertensive rats, it was the most potent and the most long-lasting.     

Differential action of KR‐31378, a novel potassium channel activator,on cardioprotective and hemodynamic effects

The cardioprotective and hemodynamic effects of KR‐31378, a highly cardioselective ATP‐sensitive potassium channel activator with minimal hypotensive effect, were evaluated in rats and dogs, and compared with those of BMS‐191095 and lemakalim. KR‐31378 did not show any significant effect on methoxamine‐induced aortic constriction up to doses of 300 μM, whereas BMS 191095 produced a moderately potent relaxant effect (IC₅₀: 9.0 μM). In conscious rats, KR‐31378 slightly increased blood pressure only at high dose (100 mg/kg, iv), unlike BMS‐191095 that dose‐dependently decreased blood pressure (ED₂₀: 2.03 mg/kg). In anesthetized beagle dogs, KR‐31378 was approximately 100‐fold less potent than BMS‐191095 for most hemodynamic parameters (iv ED₂₀ for blood pressure lowering: 33.7 and 0.37 mg/kg, respectively). In anesthetized rats subjected to 45‐min coronary occlusion and 90‐min reperfusion, KR‐31378 (iv) dose‐dependently reduced the infarct zone from 58.6% to 42.1%, 36.6%, and 34.3% for 0.1, 0.3, and 1.0 mg/kg, respectively (P < 0.05), the effects being comparable to those of BMS 191095. In anesthetized beagle dogs that underwent 2‐h occlusion followed by 4.5‐h reperfusion, KR‐31378 (2 mg/kg, iv infusion) markedly reduced the infarct zone from 48.7% in controls to 19.1% at a dose of 2 mg/kg (P < 0.05). The reduction in infarct zone afforded by KR‐31378 in rats was inhibited by pretreatment with selective ATP‐sensitive potassium channel blockers, sodium 5‐hydroxydecanoate and glibenclamide. These results indicate that KR‐31378 is a potent cardioprotective agent with potentially minimal hypotensive effects. Thus, it could be potentially useful in the prevention and treatment of acute myocardial infarction. Drug Dev. Res. 54:182–190, 2001. © 2002 Wiley‐Liss, Inc.     

The central sympatho-inhibitory effect of 5,6-dihydroxy-2-dimethylaminotetralin (M7) is mediated by α2-adrenoceptors

M7 (5,6-dihydroxy-2-dimethylaminotetralin) produces in anesthetized rats a hypotensive response previously attributed to peripheral dopaminergic mechanisms. We re-examined the effects of this drug on arterial blood pressure, heart rate and sympathetic nerve activity in anesthetized rats and dogs. M7 (1–100 μg/kg i.v.) produced in the rats transient dose-dependent pressor effects, with bradycardia and sympatho-inhibition, followed by long-lasting dose-dependent hypotension, bradycardia and sympatho-inhibition. The sympatho-inhibitory and hypotensive effects were comparable in baroreceptor-denervated rats and were reversed by idazoxan (0.1 mg/kg i.v.). The sympatho-inhibitory response induced by M7 (1–100 μg/kg) was prevented by treatment with the specific α₂-adrenoceptor antagonist, 2-methoxy-idazoxan (0.03 mg/kg i.v.). This central effect of M7 was not altered by treatment with the α₁-adrenoceptor antagonist, prazosin (0.1 mg/kg i.v.) and was reduced by treatment with the α₂-adrenoceptor antagonists, yohimbine (1 mg/kg i.v.) or idazoxan (0.3 mg/kg i.v.), and the dopaminergic antagonists, haloperidol (0.5 mg/kg i.v.) or sulpiride (3 mg/kg i.v.). Bilateral microinjections of M7 (0.3–3 nmol) into the rostroventral medulla in the rat produced dose-dependent hypotension, bradycardia and sympathetic nerve inhibition which were reversed and prevented by bilateral microinjection of 2-methoxy-idazoxan (1 nmol) into the same sites. Microinjections of 2-methoxy-idazoxan into the rostroventral medulla also inhibited the central effects of M7 at 0.03 mg/kg i.v. In anesthetized dogs, M7 administered into the cisterna magna (1–10 μg/kg) reduced arterial blood pressure, heart rate and sympathetic nerve activity; these effects were reversed by administration of 2-methoxy-idazoxan (0.03 mg/kg i.v.). In conclusion, M7, a rigid catecholamine, produces a potent central sympatho-inhibitory and hypotensive effect by activation of α₂-adrenoceptors.     

莲子心生物碱Nn-9的降压机制

蓮子心非結晶生物碱Nn-9对麻醉猫靜脉注射1-2毫克/公斤可降低原血压水平約50%,維持2-3小时。狗血压于1/2小时卽恢复,兔子不降压。有快速耐受性。經苯海拉明及异丙嗪处理猫再注射Nn-9碱2—3.5毫克/公斤,降压作用明显減弱。对靜脉注射組織胺引起的降压被Nn-9所減弱。猫靜脉注射2毫克/公斤的Nn-9后,血压下降伴随脑血管阻力減低,动脉注射0.2毫克/公斤使脑血流及后肢血流均增加,血管阻力減低。脊猫靜脉注射2毫克/公斤,有明显的降压出现。靜脉注射腎上腺素、去甲腎上腺素及脑垂体后叶素或在第七頸椎以下加高脊髓腔压所引起的升压反应均被抑制,历1/2—1小时恢复。电刺激頸交感神經节节前纤維所致的瞬膜收縮也受到抑制。对副交感神經节及M-胆碱反应系統无明显影响。頸动脉注射药液也出现降压,并抑制頸总动脉血流阻断所引起的升压反应。总結实驗結果,Nn-9的降压机制主要是释放組織胺,使外周血管扩张,其次神經因素也有关。