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。     

抗心律失常药常咯啉的临床药代动力学

11名心律失常患者,静脉滴注CRL(55 μg/kg/min)60min的峰浓度为3.6±0.6μg/ml。其中8名PVBs患者滴注后26±9 min,PVBs完全消失,血浆中CRL有效浓度为2.6±0.7μg/ml。停滴后血药浓度迅速下降,降至2.0±0.6μg/ml时PVBs又复出现。3名结性早搏病人无效。药代动力学特性表征为单室模型,动力学参数:K=0.032±0.011 min^-1;t_1/2=24±13 min;V_d=0.43±0.19 L/kg。健康志愿者6人,一次iv常咯啉50 mg,继以40μg/kg/min静滴55 min,血药浓度的范围在2.7～3.2μg/ml。对ECG和血压无明显变化。     

葛根对β-肾上腺素能受体阻滞作用的研究

本文报告了葛根浸膏具有较为广泛而显著的β-受体阻滞效应。且对β_1-受体的作用强于β_2-受体。 相当于0.5～5mg/ml或750mg/kg的葛根能分别对抗异丙肾上腺素0.17～1.7μg/ml或10μg/kg诱发的离体或在体心脏的兴奋作用。此外,相当于750mg/kg的葛根除能阻滞10μg/kg异丙肾上腺素及肾上腺素舒血管(β-受体效应)所致的降压作用外,尚能降低正常心率(平均下降43.7％)及血压(平均下降40±6mmHg)的作用,这些结果为葛根用来缓解心绞痛,治疗快速型心律失常及高血压等提供了根据。 将葛根(750mg/kg)与心得宁(0.1mg/kg)抗异丙肾上腺素(10μg/kg)所致的β-受体效应加以比较,表明两者作用大体相似,减慢心率的作用心得宁似乎稍强于葛根。降压作用葛根略优于心得宁,且葛根无明显的抑制心脏的作用。 根据上述事实,可以认为葛根是一种有效的β-受体阻滞剂。     

静脉滴注硝酸甘油治疗高血压急症60例的疗效和安全性观察

目的评估静脉滴注硝酸甘油治疗高血压急症的降压疗效及安全性。方法60例高血压急症患者接受硝酸甘油(20～80μg/分)静脉滴注治疗治疗。结果治疗前血压为26±2.4kPa/16±1.2kPa,硝酸甘油治疗2h后100%患者平均血压下降15%～25%,治疗6h后血压控制在21.3/13kPa以下者为100%,硝酸甘油降压起效快且无低血压现象发生。结论硝酸甘油治疗高血压急症有效、安全。     

依托咪酯的药理和作为静脉全麻新药应用于临床

依托咪酯“批号工03”经动物实验证实:(1)猕猴中全麻持续时间8±3min和苏醒时间20±5min。(2)家兔分别给以0.25mg/kg或1.50mg/kg,前者ECG、HR和MAP(动脉均压)无明显变化,后者HR显著减慢(p<0.01)和MAP明显升高,且ECG示P-R间期延长和P波平坦。(3)小鼠按双盲法与“批号标C1”作对照,LD_(50)/ED_(50)无显著差别。 依托咪酯“批号工03”经临床应用368例证实了:(1)作用启效时间45±15s、作用持续时间9±3min和清醒3±1min。(2)为了避免气管插管可引起MAP升高和HR增快,诱导剂量以400-500μg/kg为宜。(3)静注顺序分芬太尼2μg/kg-依托咪酯-琥珀胆碱2mg/kg或潘库溴铵100±20μg/kg芬太尼-依托咪酯,后者更可取。(4)能促使血糖升高,对琥珀胆碱所导致高钾血症无助。(5)与既知的静脉全麻药比较,对血流动力学的影响最轻微。     

乌菊降压丸药效学实验

目的 :对乌菊降压丸的药理作用进行实验研究。方法 :以正常血压大鼠和自发性高血压大鼠 (SHR )的血压和心率为动物模型 ,观察乌菊降压丸的药效作用。空白对照组给予相应量的0 5 %羧甲基纤维素钠 ;阳性对照组给予牛黄降压丸2g/kg;实验组给予乌菊降压丸 ,高、中、低剂量分别为1 2、0 6、0 2g/kg。灌胃给药 ,qd ,连续15d。分别观察并记录给药后10、20、30、45、60、90、120、240min时的血压和心率变化。结果 :乌菊降压丸高、中剂量对SHR分别在20、30min起效 ,血压开始下降 ,心率开始减慢 ,分别维持3h和1h ,4h和2h恢复原来水平。结论 :乌菊降压丸对正常血压大鼠的血压和心率无明显影响 (P>0 05) ,但有一定降低趋势 ;对SHR连续给药15d后具有明显降压作用和减慢心率的作用 (P<0 05) ;高剂量组有较好的降压效果     

硝苯吡啶和间硝苯啶扩血管降压作用的比较

本实验比较了硝苯吡啶与间硝苯啶的降压作用与持续时间、血流动力学效应及光稳定性。结果表明,二者均具有明显的扩血管降压作用。硝苯吡啶和间硝苯啶引起麻醉大鼠血压下降的ED_(50)分别为0.25±0.13和0.20±0.07μmol/kg;iv 50μg/kg其作用持续时间为68±48和58±30min;间硝苯啶对光稳定,而硝苯吡啶曝光3h则丧失降压活性。     

口服头孢拉定在血透病员中的药物动力学及给药方案

本文报道4倒尿毒症病员进行血透治疗时口服500mg头孢拉定,透析期内病员体内及透析器的药物动力学参数分别为V_B0.11±0.06和1.1±1.5L/kg;CL0.040±0.024和0.16±0.20L/(kg·h);t_(1/2)1.90±0.26和9±5h。5h透析病员体内药量下降64％,透析器可清除41％药物。表明头孢拉定能被透析清除。3例病员血透前口服500mg头孢拉定的血浓峰值为52.91μg/ml,血透后再给500mg补充剂量,在再次给药前血浓值仍有51μg/ml。     

槐定碱对正常大鼠心脏功能的影响

正常大鼠静脉注射槐定碱(Sophoridine Sri,20mg/kg)1min后,左心室内压力变化速率最大值(±dP/dt_(max)),左室内压力峰值(LVSP),动脉压均值及左室O负荷时收缩成份最大速度(V_(max))分别增加19.5%,13.1％,14.8%和28.2％,持续5～7min上述指标与给药前及生理盐水对照组比较,差异显著。心率(HR)减慢,但无统计学差异。肾上腺素(0.16μg/kg,iv)对±LVdP/dt_(max)和V_(max)的影响除iv后0.5min外,与Sri比较无统计学差异,作用比Sri短暂。Sri iv后1～3min内,由于MAP升高,因此心肌耗氧指数(MVO_2I)亦增高,但明显低于肾上腺素组。本研究结果表明:Sri增强心肌收缩力作用较肾上腺素持久,且不加快心率,而升高动脉压和MVO_2I的作用明显低于肾上腺素。     

静脉应用胺碘酮转复阵发性心房颤动24例疗效观察

目的观察静脉注射胺碘酮转复阵发性心房颤动(房颤)的疗效及安全性。方法24例阵发性房颤患者,首剂负荷量胺碘酮3mg/kg～5mg/kg,10min内缓慢静脉注射,继之以1.0mg/min～1.5mg/min的速度维持静脉滴注,24h后依病情逐渐减量,可维持静脉滴注72h,静脉应用胺碘酮24h后加用口服胺碘酮600mg/d,30min未转复者可给予1.5mg/kg～3mg/kg的追加负荷量。结果静脉应用胺碘酮转复阵发性房颤的有效率可达79.2%,平均转复时间为(35.6±20.8)min。平均转复用药剂量(250±100)mg。1例出现一过性窦性心动过缓,1例出现血压下降、恶心、呕吐,余未见其他严重不良反应发生。结论静脉应用胺碘酮终止阵发性房颤是安全有效的急诊药物疗法。     

碘化二甲基木防己的降压作用

本文报告碘化二甲基木防己碱(DTI)降压作用的研究。DTI给麻醉动物静脉注射,对狗0.05～0.1 mg/kg使血压下降42.3～61.5%,持续1小时左右恢复至原血压水平;对猫0.00625～0.0125 mg/kg使血压下降26.5～43.5%,持续2～4小时恢复至原血压水平;对兔0.005～0.01 mg/kg使血压下降24.3～61.0%,5小时不能恢复至原血压水平;0.5～1.0 mg/kg使大鼠血压下降27.2～41.1%。DTI的降压作用机制主要与其对神经节的阻断作用有关。本药对小鼠口服和静注的LD₅₀分别为522.0 mg/kg及2.23 mg/kg。     

Central noradrenergic neurones and the cardiovascular actions of clonidine in the rabbit

1. Clonidine (1 mug/kg), given by intracisternal injection to anaesthetized rabbits, lowered mean arterial blood pressure by 33 mmHg and heart rate by 32 beats/min.2. In animals pre-treated with 6-hydroxydopamine (6-OHD 500 mug/kg intracisternally) 7-10 days before, intracisternal clonidine (1 mug/kg) reduced mean arterial blood pressure by only 2.5 mmHg and heart rate by 4 beats/minute.3. The hypotensive action of intravenous clonidine was reduced to 49% of control by pre-treatment with intracisternal 6-OHD. In unanaesthetized normal animals intravenous clonidine (30 mug/kg) lowered mean arterial blood pressure by 19.3 mmHg, while after 6-OHD it fell only 9.4 mmHg.4. These studies suggest that the central hypotensive effect of clonidine is dependent on the integrity of central monoaminergic neurones.     

Hypotensive effect in dogs and rats of intravenous injections of the alpha 1-adrenoreceptor antagonist benoxathian

The hypotensive effect of the alpha 1-adrenoreceptor antagonist benoxathian has been evaluated in rats and dogs, in comparison to that evoked by WB 4101 and prazosin. In anaesthetized dogs, i.v. injection of benoxathian (25-100 micrograms/kg), WB 4101 (5-25 micrograms/kg) and prazosin (50 micrograms/kg) produced an immediate fall in diastolic blood pressure, which reached a maximum at about 30 sec after drug administration. Whereas the hypotensive effect of prazosin persisted up to 3 hr following injection, the effect of both benoxathian and WB 4101 completely disappeared after 30-60 min. The hypotensive effect of benoxathian was dose-dependent. Pressor responses to i.v. noradrenaline (5 micrograms/kg), adrenaline (5 micrograms/kg) and phenylephrine (20 micrograms/kg) were markedly inhibited (60-75%) by benoxathian (100 micrograms/kg) whilst the pressor response to angiotensin II (0.05 micrograms/kg) was not reduced, but indeed slightly increased. The hypotensive effect of benoxathian (100 micrograms/kg) was abolished following pre-treatment with prazosin (50 micrograms/kg) or hexamethonium (1000 micrograms/kg). In anaesthetized rats similar results were obtained although recovery in blood pressure from the initial drop after i.v. injection of the drugs was slower than in dogs. Benoxathian was slightly more toxic than WB 4101 in rats. In conclusion, present findings show that benoxathian causes a profound hypotensive effect in dogs and in rats through postsynaptic alpha-adrenoreceptor blockade; however its effect, as well as that of WB 4101, is shorter lasting than that of prazosin.     

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.     

Effect of lisinopril and isosorbide-5-mononitrate on hemodynamics and mortality in rats with permanent coronary artery occlusion.

We studied the hemodynamic effects of lisinopril and isosorbide-5-mononitrate in rats with permanent coronary occlusion. Rats (n = 35) underwent left coronary occlusion, and ECGs were recorded before and after occlusion. Ventricular arrhythmias were observed in 57% (20 of 35) of animals. Treatment was given immediately after coronary occlusion and for 2 subsequent days. The control group received 100 mg/kg lactose (i.e., 80% vehicle for isosorbide-5-mononitrate). Lisinopril (100 mg/kg body weight) and isosorbide-5-mononitrate (400 mg/kg body weight) reduced systolic blood pressure (SBP) from 134 +/- 9 to 115 +/- 9 mm Hg (p less than 0.05) and from 137 +/- 9 to 126 +/- 9 mm Hg, respectively; the hypotensive effect lasted 2-3 days. No effect on BP was noted in the control group. Overall mortality was 23%; 8 of 35 animals died within 10-15 min of coronary occlusion. Survival after 4 weeks was similar in each group (approximately 80%). Left ventricular pressure (LVP) was measured 4 weeks after coronary artery occlusion and was similar in each group. However, dP/dt was lower in hearts with infarction than in hearts with none (12,608 +/- 906 vs. 8,992 +/- 1,242 mm Hg/s). The extent of the infarction was the same in groups with coronary artery occlusion. Lisinopril is more effective than isosorbide-5-mononitrate in reducing BP after acute myocardial infarction (AMI). Medium-term survival (4 weeks) is not jeopardized by effective treatment with angiotensin-converting enzyme (ACE) inhibitors or long-acting nitrates.     

苦马豆总黄酮甙的降压作用及其机理

麻醉动物、清醒动物以及自发性高血压大鼠,iv苦马豆总黄酮甙后,均有显著的降压作用,起效快,持续时间短。降压机理与交感神经节阻断作用和直接扩张血管作用有关。血流动力学实验表明,苦马豆总黄酮甙对心肌收缩力和心率均无明显影响。由于外周扩血管作用而使总外周阻力明显降低。     

Assessment of the acute cardiotoxic potential of sodium nitroprusside infusions in Beagle dogs

Fourteen unanesthetized dogs were infused with nitroprusside for 30 min (10 or 100 μg/kg/min), 3 hr (25 μg/kg/min), or 6 hr (12.5 or 25.0 μg/kg/min) on two consecutive days. Two animals died following the high-dose 6-hr infusion. Minimal left papillary muscle necrosis was detected in one of the four hearts taken from the dogs infused with 12.5 μg/kg/min for 6 hr. In four anesthetized dogs the 12.5- and 25.0-μg/kg/min doses depressed blood pressure by an average of 20–27% and 45–48%, respectively. Both doses increased heart rate approximately 20%. The effect of 60-min nitroprusside infusion of 3.5–28.0 μg/kg/min on a variety of cardiovascular functions was assessed in 10 dogs. The most consistently observed changes were a dose-related decrease in blood pressure (19–50%) and an increase in coronary blood flow (30–300%). In spite of the hypotensive response, only minor changes in heart rate, cardiac output, and ventricular force of contraction occurred. The results indicate that the secondary cardiovascular actions of nitroprusside are not as prominent as with other vasodilators. Consequently nitroprusside appears to possess less acute cardiotoxic potential than other agents such as minoxidil, diazoxide, or hydralazine.     

Effect of acute and subchronic subcutaneous urocortin on blood pressure and food consumption in ob/ob mice

Corticotropin-releasing factor and urocortin belong to a hypothalamic peptide family thought to be important in appetite regulation. The present study compared the appetite-suppressant effect of subcutaneous urocortin in obese mice to its cardiovascular effects. Acutely, urocortin (100 nmol/kg iv) reduced blood pressure and increased heart rate in urethane anesthetized nonobese mice; effects similar to those produced by subcutaneous urocortin (10 and 100 nmol/kg sc) in nonobese and ob/ob mice. Over this same dose range (10-100 nmol/kg sc), urocortin dramatically inhibited food consumption in the ob/ob mouse. To determine if the acute hypotensive effect of urocortin (10 nmol/kg sc) in the ob/ob mouse persisted after repeated urocortin administration, animals were pretreated for 3 days with urocortin (10 nmol/kg sc) or vehicle. Following urocortin pretreatment, urocortin-induced hypotension was similar to the effect in vehicle pretreated mice. However, urocortin-induced appetite suppression was reduced following 3 days of pretreatment with urocortin (10 nmol/kg sc) to ob/ob mice. These data suggest that the hypotensive and appetite-suppressant effects of urocortin are mediated by different mechanisms and tolerance to the hypotension did not readily occur in obese animals.     

Effect of vasodilator drugs on coronary occlusion and reperfusion arrhythmias in anesthetized dogs

The effect of vasodilator drugs on the incidence of ventricular arrhythmias induced during 30 min of occlusion and 15 min of reperfusion of the left anterior descending coronary artery (LAD) was studied in 65 pentobarbital-anesthetized open-chest dogs. Intravenous administration of captopril (0.5 mg/kg), enalapril (0.5 mg/kg), felodipine (4 micrograms/kg), or ketanserin (0.1 mg/kg) 30 min before LAD occlusion reduced mean arterial blood pressure by 15.5 +/- 0.6% (mean +/- SEM). Nifedipine (5 micrograms/kg bolus + 1 microgram/kg min-1) infusion reduced mean arterial blood pressure by 24.8 +/- 1.8%. In none of the dogs was the diastolic blood pressure reduced below 70 mm Hg. During LAD occlusion, reduction in arterial blood pressure by these drugs was associated with a reduced incidence of ventricular premature depolarizations, ventricular tachycardia, and ventricular fibrillation (VF). During LAD reperfusion, the incidence of VF in saline-treated animals was 6/9, whereas for captopril it was 6/9, enalapril 1/9, felodipine 7/9, nifedipine 3/8, and ketanserin 3/9 animals. Thus, only enalapril significantly lowered the incidence of VF (p less than 0.05). The mechanism responsible for this antifibrillatory effect of enalapril is unknown. The muscle mass of the left ventricle supplied by the LAD distal to the site of occlusion in dogs which survived was similar to that of dogs which developed ventricular fibrillation.