福辛普利对去窦弓神经大鼠器官损伤的保护作用

目的研究血压波动性在福辛普利治疗去窦弓神经大鼠器官保护中的重要作用。方法在去窦弓神经(SAD)大鼠饲料中给予福辛普利15 mg·kg^-1·d^-1（根据体重和每日消耗的饲料总量计算，每周调整1次），16周后在清醒状态下记录24　h血压波动性，用光镜和计算机图象分析技术观察心脏、肾脏和胸主动脉的组织病理学改变。结果与SAD大鼠相比，福辛普利治疗组大鼠的血压波动性明显降低，左心室壁厚、肾小球硬化积分、心肌胶原容积分数与血压波动性呈正相关，福辛普利可明显减轻去窦弓神经大鼠引起的器官损伤。结论福辛普利长期治疗可有效减轻去窦弓神经大鼠的器官损伤。降低血压波动性在福辛普利的器官保护中可能具有重要的作用。     

利尿剂协同ACE抑制剂降压作用的实验研究

目的研究利尿剂氢氯噻嗪与ACE抑制剂依那普利联合对自发性高血压大鼠降低血压及血压波动性的协同作用,评价两药不同比例配伍时的协同作用效果。方法采用清醒动物血压监测技术,监测自发性高血压大鼠分别通过胃瘘管给予0.8%的羧甲基纤维素钠(CMC)、氢氯噻嗪(10mg/kg)、依那普利(2,4,8mg/kg)、氢氯噻嗪和依那普利混悬液(10+2、10+4、10+8mg/kg)后血压及血压波动性的变化。结果与对照组比较氢氯噻嗪和依那普利合用时可以明显的降低血压及血压波动性。大剂量合用时降低收缩压55mmHg(1mmHg=0.133kPa),大于两药单独使用时的降压幅度。q值在氢氯噻嗪+依那普利10+4mg/kg时最大。结论利尿剂与ACE抑制剂合用对降低血压及血压波动性具有明显的协同作用,氢氯噻嗪:依那普利为5:2时协同作用最为明显。     

去窦弓神经大鼠体内血管舒/缩功能的测定

目的　研究完全及部分去窦弓神经大鼠术后体内血管收缩 /舒张功能的改变。方法　用Sprague Dawley大鼠分别去除颈动脉窦神经 (SD)或主动脉神经支配 (AD) ,以及完全去除窦 弓神经支配 (SAD)。术后急性期 (1wk)、慢性期(18wk)在清醒、自由活动状态下分别测定动脉血压、心率及血压波动性、心率波动性。并分别测定上述大鼠ABR功能(ABR HP和ABR BP)。对术后 18wk的完全及部分去窦弓神经大鼠 ,通过静脉累积注射去氧肾上腺素以及硝普钠分别测定体内动脉收缩 /舒张功能。结果　术后 1wk ,SAD及AD大鼠动脉血压显著升高 ;术后 18wk ,SAD大鼠 2 4h血压平均值与对照假手术大鼠相比无差异 ,而AD大鼠血压仍较对照组明显升高。SD大鼠的血压、心率在术后 1wk及术后 18wk均无升高。术后 18wk ,SAD及AD大鼠 2 4h血压波动性较对照组大鼠升高。术后 1wk及 18wk的SAD大鼠ABR功能较对照组明显降低 ,AD大鼠ABR功能也低于对照组 ,而SD大鼠ABR功能与假手术大鼠间无差异性。术后 18wkSAD、AD和SD大鼠SBPmax(注射去氧肾上腺素后 )及DBPmin(注射硝普钠后 )较对照组大鼠均明显上升。完全及部分去窦弓神经大鼠的SBPmax和DBPmin分别与ABR功能呈负相关 ;SAD、AD及SD大鼠的ABR功能与血压波动性呈密切负相关。结论　去窦弓神经术后慢性期大     

去窦弓神经大鼠的心血管及肾脏的形态学改变(英文)

目的　研究去窦弓神经 (SAD)对正常血压大鼠的血流动力学及心、肾、血管等器官病理形态学的影响。方法　采用SD大鼠施行SAD手术 ,术后 18周行股动脉插管 ,在清醒、自由活动状态下计算机实时记录 2 4h动脉收缩压、舒张压和心率 ,并计算血压波动性 (BPV)和心率波动性 (HRV)。处死动物后 ,取心、脑、肾及脾观察大体及光学显微镜下结构变化。结果　SAD术后 18周 ,SAD大鼠的血压和心率水平与假手术组相比无显著差异 ,但 2 4hBPV明显高于假手术组 ,HRV明显低于假手术组 ;大鼠心、肾及血管有明显的类似于高血压靶器官损伤的病理改变。结论　SAD可使大鼠的心、肾和血管发生类似于高血压靶器官损伤的病理改变。     

新型正性肌力活性物PHR0007对大鼠血压和心电图的影响

目的探讨新型正性肌力活性物PHR0007(三唑并二氢喹啉衍生物)对大鼠动脉血压和心电图的影响和作用机制。方法经股动脉插管连接压力换能器和用针状电极连接标准肢体导联,利用BL-420S生物机能实验系统观察给药前和静脉单用PHR0007(0.1、0.3、1.0μg.kg-1)或米力农(3.8μg.kg-1),以及合用PHR0007(0.1μg.kg-1)和米力农(3.8μg.kg-1)后1 h之内的股动脉血压和肢体标准Ⅱ导联心电图变化。结果与给药前比较,注射PHR0007后0.10~0.75 h内收缩压显著提高(P<0.05)。注射米力农后0.10~0.25 h内收缩压也明显增高(P<0.05)。合用米力农和PHR0007后0.10~0.75 h内收缩压虽然升高(P<0.05),但较单用PHR0007或米力农无明显差异(P>0.05)。0.1μg.kg-1PHR0007使心率减慢(P<0.05)。不同浓度的PHR0007使QT间期延长(P<0.05),且在低剂量更加明显。各种处理因素对舒张压和PR间期无显著性影响。结论类似米力农,PHR0007对大鼠具有强心和扩血管作用。     

苯磺酸左旋氨氯地平联合卡托普利对原发性高血压患者的治疗体会

目的观察苯磺酸左旋氨氯地平联合卡托普利治疗原发性高血压的临床疗效。方法128例原发性高血压患者随机分为两组,64例给予苯磺酸左旋氨氯地平联合卡托普利治疗,64例单用卡托普利治疗,两组患者均给予治疗6周,观察2组患者治疗前后的血压变化及不良反应情况。结果治疗后两组患者的收缩压、舒张压均明显下降（P〈0．05）,与卡托普利组比较,苯磺酸左旋氨氯地平和卡托普利联合用药组治疗后患者收缩胩和舒张压下降的水平更明显（P〈0．05）;苯磺酸左旋氨氯地平和卡托普利联合用药治疗组总有效率92．19％,而卡托普利组的总有效率71．88％,联合用药治疗组总有效率明显高于卡托普利组,且差异有统计学意义（P〈0．05）。结论原发性高血压患者采用苯磺酸左旋氨氯地平联合卡托普利治疗组降压效果优于单用卡托普利治疗组。     

萘哌地尔衍生物BWYJ对大鼠血压及猫血流动力学的影响

目的:观察萘哌地尔衍生物BWYJ对高血压模型和正常大鼠血压及猫血流动力学的影响。方法:分别对高血压和正常大鼠静脉及灌胃给药,观察血压变化;利用麻醉开胸测定猫血流动力学的变化;采用侧脑室给药、猫在体瞬膜神经肌肉标本初步探讨降压机制。结果:BWYJ1.2及2.4mg·kg-1iv,降低正常及高血压大鼠收缩压(SAP)和舒张压(DAP),且随剂量的增加效应增加,作用时间延长。BWYJ10、20及40mg·kg-1灌胃给药,降低清醒正常大鼠SAP(最大效应分别下降4.6%、13.0%、16.8%)和DAP(分别下降7.1%、17.9%、20.5%),3h后恢复。BWYJ5、10及20mg·kg-1灌胃清醒高血压大鼠,降低SAP(下降7.3%、16.5%、20.4%)和DAP(8.5%、14.8%、24.5%),强于正常大鼠且时间明显延长。麻醉猫十二直肠给药,BWYJ2.5mg·kg-1仅DAP、LVWI降低,BWYJ5mg·kg-1使SAP、DAP、TPR、±dp/dtmax及LVWI明显降低,其他无明显变化。结论:BWYJ静脉或灌胃给药对正常和肾性高血压大鼠产生降压作用,降压作用与中枢、神经节无关。     

酮色林和坎地沙坦对清醒自由活动自发高血压大鼠压力反射功能的影响

目的比较酮色林和坎地沙坦对清醒自由活动自发高血压大鼠压力反射功能的影响。方法采用计算机化清醒自由活动大鼠血压监测方法测定血压、血压波动性和心动周期;用Smyth法测定压力反射功能敏感性。酮色林和坎地沙坦均分为1.0、3.0、10.0 mg.kg-13个剂量组。结果酮色林(1.0、3.0、10.0 mg.kg-1)可剂量依赖性地降低清醒自由活动自发高血压大鼠的血压,同时可显著改善其压力反射功能,但改善压力反射功能的作用无剂量依赖性;坎地沙坦(1.0、3.0、10.0 mg.kg-1)可剂量依赖性地降低清醒自由活动自发高血压大鼠的血压,但各剂量组对其压力反射功能均无显著影响。结论酮色林和坎地沙坦均可剂量依赖性降低清醒自由活动自发高血压大鼠的血压;酮色林的改善压力反射功能、稳定血压的作用优于坎地沙坦。     

ketanserin对慢性心肌梗死大鼠血流动力学的影响

目的　研究ketanserin对慢性心肌梗死大鼠血流动力学的影响。方法　设假手术组、心肌梗死组和心肌梗死治疗组。治疗组在冠脉结扎后饮水中给予ketanserin 10mg·kg-1·d-1,持续 4～ 5wk。在清醒自由活动条件下连续监测血压 ,并采用改良Symth法测定动脉压力感受性反射敏感性(BRS)。结果　与假手术组比较 ,心肌梗死大鼠血压下降、心动间期波动性 (HPV )升高、BRS降低 ,而血压波动性(BPV)和心动间期无明显改变。ketanserin长期治疗可降低心肌梗死大鼠的血压、BPV和改善BRS。心肌梗死组室性心律失常发生率为 60 % (12 / 2 0 ) ,经ketanserin治疗后降至2 8 6% (6/ 2 1)。治疗或未治疗心肌梗死大鼠如果存在心律失常 ,则HPV升高 ,否则正常。结论　ketanserin可能作为改善心肌梗死预后的治疗药物。心肌梗死大鼠HPV增加与心律失常有关     

尼群地平对缺氧性右心室肥大的预防和治疗作用(英文)

目的:本文探讨尼群地平对缺氧性右心室肥大的影响。方法:慢性间断性减压引起缺氧性右心室肥大,用右心室重量指数,心肌超微结构变化来评价尼群地平疗效。结果:慢性缺氧大鼠右心室收缩压及右心室重量指数明显增加及心肌超微结构变化。无论在减压开始或已发展右心室肥大后,服用尼群地平均可降低右室收缩压和右室重量指数及促使心肌超微结构正常。结论:尼群地平可预防和减轻缺氧性右心室肥大。     

Effects of combination therapy with atenolol and amlodipine on blood pressure control and stroke prevention in stroke-prone spontaneously hypertensive rats

Aim： To test the effects of atenolol and amlodipine, either alone or in combination, on blood pressure, blood pressure variability （BPV）, baroreflex sensitivity （BRS）, and the prevalence of stroke in stroke-prone spontaneously hypertensive rats （SHR-SP）. Methods： In the first set of the study, 24 8-month-old, female SHR-SP rats were randomly divided into 3 groups. Blood pressure, heart period, and BRS were determined before and after the intragastric administration of atenolol （10 mg/kg） and amlodipine （1.0 mg/kg）, either alone or in combination. In the second set of the study, 40 male and 40 female rats were randomly assigned to 1 of the following 4 groups： control, atenolol （10 mg·kg^-1·d^-1）, amlodipine （1.0 mg·kg^-1·d^-1）, and both （10 male and 10 female in each group）. The stroke incident and survival time were recorded. Results： Atenolol and amlodipine, either alone or in combination, significantly decreased blood pressure, with the exception of the amlodipine-induced effect on diastolic blood pressure. Meanwhile, only the combination treatment significantly decreased the BPV levels for the same period. The q-values calculated by the probability sum analysis were 1.17 and 2.67 for systolic and diastolic blood pressure, respectively, and were 2.48 and 2.10 for systolic and diastolic BPV, respectively, following administration. Neither drug exhibited any significant effect on BRS. Atenolol and amlodipine, either alone or in combination, significantly increased the lifespan of SHR-SP, with the best effect elicited by the combination therapy. Conclusion： A significant synergism exists between atenolol and amlodipine in lowering and stabilizing blood pressure in SHR-SP. Combination therapy may be an optimal strategy for the prevention of stroke in hypertension.     

Synergism of hydrochlorothiazide and nitrendipine on reduction of blood pressure and blood pressure variability in spontaneously hypertensive rats

AIM: To investigate the possible synergism of hydrochlorothiazide and nitrendipine on reducing both blood pressure (BP) and blood pressure variability (BPV) in spontaneously hypertensive rats (SHR). METHODS: Seventy animals were randomly divided into seven groups. The doses were 5 and 10 mg/kg for nitrendipine, 10 and 20 mg/kg for hydrochlorothiazide and 10 + 5, 20 + 10 mg/kg, respectively, for the combination of these two drugs and 0.8% carboxymethylcellulose as control. The drugs were given via a catheter of gastric fistula. BP was then continuously recorded for 5 h from 1 h before drug administration to the end of 4th hour after drug administration, in conscious and freely moving rats. RESULTS: The effects on both BP and BPV reduction of the combination of hydrochlorothiazide and nitrendipine were greater than the single drug in SHR. The two drugs possessed an obvious synergism on both systolic blood pressure (q = 1.79 with small dose and q = 1.23 with large dose) and systolic blood pressure variability reduction (q = 1.79 with small dose and q = 1.39 with large dose) in SHR. CONCLUSION: The present work clearly demonstrated that there was a synergistic effect between hydrochlorothiazide and nitrendipine in lowering and stabilizing BP in SHR.     

多沙唑嗪对映体对大鼠血压和排尿功能的影响

目的观察十二指肠给予多沙唑嗪(rac-DOX)及其对映体(S-DOX、R-DOX)对麻醉大鼠血压和膀胱排尿功能的影响。方法采用八道生理仪记录麻醉大鼠颈总动脉血压、心率以及膀胱排尿压、排尿间隔,并测量排尿量。结果十二指肠给予S-DOX、R-DOX和rac-DOX均可剂量依赖性降低颈总动脉收缩压、舒张压和平均动脉压,1.0mg.kg-1时3者对平均动脉压的降低幅度分别达到23.5%±4.6%、38.5%±8.9%和42.6%±7.5%,3者降低平均动脉压的ED30值依次为(2.0±0.8)、(0.6±0.7)、(0.6±0.5)mg.kg-1。S-DOX降低收缩压、舒张压和平均动脉压的作用均弱于rac-DOX和R-DOX(P<0.05),rac-DOX与R-DOX的降压作用差异无显著性(P>0.05)。rac-DOX在0.1～3.0mg.kg-1剂量范围内剂量依赖性抑制麻醉大鼠心率,而S-DOX和R-DOX仅在3.0mg.kg-1剂量时对心率有抑制作用。十二指肠给予S-DOX、R-DOX和rac-DOX均剂量依赖性降低麻醉大鼠膀胱排尿压,3种药物对排尿压的最大降低幅度分别为13.4%±5.7%、14.5%±11.0%和10.9%±7.6%,3者降低排尿压的作用差异无显著性(P>0.05)。与S-DOX相比,R-DOX可缩短排尿间隔并减少排尿量(P<0.05),而S-DOX和rac-DOX对排尿间隔和排尿量无影响。结论与R-DOX和rac-DOX相比,S-DOX保留了对麻醉大鼠膀胱排尿压的有利作用,减轻了对血压、心率和膀胱排尿间隔的不良影响。     

Two useful methods for evaluating antihypertensive drugs in conscious freely moving rats

INTRODUCTION Since the beginning of 1980s, a computerized tech-nique has been developed for measuring blood pressure(BP) for a long time (more than 24 h) in consciousfreely moving rats[1-5]. With this technique one can studythe cardiaovascular parameters in a physiological con-dition in rats and avoid the influences of anesthesia andstress. This technique is used not only for physiologicalstudies but also for pharmacological studies including theevaluationof antihypertensive drugs.…     

Synergistic effects of atenolol and amlodipine for lowering and stabilizing blood pressure in 2K1C renovascular hypertensive rats

AIM: To test the synergistic effects of atenolol and amlodipine on lowering blood pressure (BP) and reducing blood pressure variability (BPV) in 2-kidney, one-clip (2K1C) renovascular hypertensive rats. METHODS: Forty-eight 2K1C renovascular hypertensive rats were randomly divided into 6 groups. They were respectively given 0.8% carboxymethylcellulose sodium (control), atenolol (10.0 mg/kg), amlodipine (1.0 mg/kg), and combined atenolol and amlodipine (low dose: 5.0+0.5 mg/kg; intermediate dose: 10.0+1.0 mg/kg; high dose: 20.0+2.0 mg/kg). The drugs were given via a catheter in a gastric fistula. BP was recorded for 25 h from 1 h before drug administration to 24 h after administration. RESULTS: Compared with BP before medication, all 3 doses of combined atenolol and amlodipine significantly decreased the BP at 24 h after administration, except for the low dose on diastolic BP. Compared with the control group, all 3 doses of combined atenolol and amlodipine significantly reduced the average BP levels for the 24 h period after administration; furthermore, the high and intermediate doses also significantly decreased the BPV levels for the same period. The q values calculated by probability sum analysis for systolic and diastolic BP for the 24 h period after administration were 2.29 and 1.45, respectively, and for systolic and diastolic BPV for the same period they were 1.41 and 1.60, respectively. CONCLUSION: There is significant synergism between atenolol and amlodipine in lowering and stabilizing BP in 2K1C renovascular hypertensive rats.     

多沙唑嗪对映体对麻醉猫心血管功能的选择性作用

目的研究多沙唑嗪对映体对麻醉猫心血管功能的影响。方法采用八道生理仪记录麻醉猫股动脉血压、心率以及左心室收缩压、左心室舒张末期压和左心室内压最大变化率(±dp/dtmax)。结果十二指肠给予右旋多沙唑嗪[(+)doxazosin,(+)DOX]0.03～1.0 mg.kg-1剂量依赖性降低麻醉猫收缩压、舒张压、平均动脉压和左心室收缩压(P<0.05)。十二指肠给予同等剂量的左旋多沙唑嗪[(-)doxazosin,(-)DOX]和消旋多沙唑嗪[(±)doxazosin,(±)DOX]对麻醉猫收缩压、舒张压、平均动脉压和左心室收缩压无影响(P>0.05)。3种药物对左心室舒张末期压、左心室-dp/dt、左心室+dp/dt和心率无影响(P>0.05)。结论麻醉猫十二指肠给药时,(+)DOX降低动脉血压并抑制心室收缩功能,相同剂量的(-)DOX无作用;提示DOX的手性结构对药物的心血管效应具有明显的影响。     

尼群地平单用及其与美多洛尔合用对大鼠血压和胸主动脉环收缩的影响

<正> 近年来,在高血压病的治疗中,钙拮抗剂(如硝苯啶)与β受体阻断剂(如醋丁洛尔)的合用已引起关注.尼群地平(nitrendIpine,Nit)是一种较新的二氢吡啶类钙通道阻滞剂,美多洛尔(metoprolol,Met)是一种选择性β_1受体阻断剂.该二药的合用尚未见研究报道.本文采用麻醉大鼠观察