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     

降压避风片新老配方药理作用比较研究

目的 比较降压避风片新老配方的降压效果及作用特点.方法 选用原发性高血压大鼠(SHR)及其对照性WKY大鼠进行对比试验.实验动物分为8组:WKY大鼠组、SHR对照组、降压避风片老配方组高、中、低剂量(1.00、0.50、0.25 g药粉/kg)组、降压避风片新配方高、中、低剂量(1.00、0.50、0.25 g药粉/kg)组.降压试验采用大鼠无创血压测定仪对大鼠尾动脉进行血压测定,分为急性降压作用试验和慢性降压验.急性降压测定给药前、给药后1、3 h血压值;慢性降压测定连续给药后6、11、14 d血压值.连续给药14 d后,进行大鼠心脏超声心动试验,监测大鼠室间隔厚度、左室内径、左室后壁、射血分数、左室短轴缩短率、左心室心肌质量、左心室容量等;后腹主动脉取血,分别测定血清NO、总蛋白、白蛋白、球蛋白、丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、尿素、肌酐、葡萄糖、三酰甘油、低密度脂蛋白和血浆内皮素、肾素活性及血管紧张素Ⅱ含量.结果 急性降压试验:各剂量组均可显著降低药后3 h的收缩压(P <0.01),新老配方相应剂量间无显著差异;慢性降压试验:SHR组心率显著快于WKY组,用药后,各剂量组均无显著降低心率的效果.结论 新老配方均可平稳降低SHR血压,降压作用确切.     

藤丹胶囊对自发性高血压大鼠的降压作用

目的　观察藤丹胶囊对清醒自发性高血压大鼠 (spontaneous hypertension rats,SHR)血压和心率的影响。方法　单次及连续 1 4d每天灌服藤丹胶囊 0 .3 ,1 ,3 g· kg-1(相当于生药 ) ,并设有效药物阳性对照组 ,观察各剂量组对血压与心率的改变及恢复情况。结果　单次灌服大鼠血压呈剂量相关性降低 ,约 3 h达峰效应 ,高剂量作用维持时间超过 48h,降压同时心率无明显改变。连续 1 4d用药血压亦呈剂量相关性降低 ,每天的血压下降未见明显改变 ,表明无耐药性 ;停药后血压缓慢恢复到给药前水平 ,表明无反跳现象。结论　藤丹胶囊对SHR有明显的降压作用 ,对心率无明显影响     

白川降压胶囊对肾性高血压大鼠血压的影响

目的　观察白川降压胶囊 (BC)对肾性高血压模型大鼠的急性降压作用和对心率的影响。方法　采用颈动脉插管直接测压法测量血压和心率。结果　给予 BC 0 .1 5 ,0 .3 ,0 .6 g· kg-13 0 ,6 0 ,90 ,1 2 0 min后大鼠收缩压、舒张压均明显降低 ,与对照组比较 P <0 .0 5。 BC各剂量给药后大鼠心率无明显变化 ,与对照组比较 P >0 .0 5。结论　BC对肾性高血压大鼠具有明显的急性降压作用 ,对心率无影响     

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。     

心压平胶囊治疗高血压病的药效学研究

观察心压平胶囊对正常 SD大鼠和清醒自发高血压大鼠 ( SHR)血压、心率、心肌耗氧量的影响。结果 :十二指肠给药心压平胶囊对正常 SD大鼠有降压作用 ,对清醒 SHR也有降压作用 ;可降低正常麻醉 SD大鼠心率 ;三个剂量组对正常麻醉 SD大鼠和大剂量组 SHR有显著降低心肌耗氧量作用。     

国产硝苯地平控释片降压效果动态血压分析

目的:观察国产硝苯地平控释片的降压效果。方法:82例原发性高血压(EH)患者每天服用国产硝苯地平控释片30～60mg,疗程4～8周,均以24 h动态血压作为监测及评价方法。结果:24 h收缩压和舒张压均明显下降(P<0.01),收缩压谷峰比=89%,舒张压谷峰比=82%,对夜间血压不产生过度降压作用,对血糖、血脂、血尿酸无影响,不良反应发生率低。结论:每日服用30～60 mg国产硝苯地平控释片对EH有24 h平稳降压作用。     

盐酸埃他卡林选择性降压作用的研究

目的 :在清醒正常血压犬和“两肾一夹”肾性高血压犬 (RHD)上 ,观察不同剂量盐酸埃他卡林(iptakalimhydrochloride,Ipt)的降压作用特征 ;在清醒正常血压的Wistar大鼠和脑卒中易感型自发性高血压大鼠 (stroke pronespontaneouslyhypertensiverat,SHRsp)上 ,采用无创心功能监测方法 ,观察Ipt对心功能和血流动力学的作用特征 ,以判断其降压作用和对心功能及血流动力学的影响是否具有选择性。方法 :给清醒正常血压犬和RHD口服不同剂量的Ipt,用听诊法测量移于皮鞘内的颈总动脉血压 ,用触诊法测量心率 ,同时记录Ⅱ导联心电图。给清醒正常血压大鼠和SHRsp静脉注射相同剂量的Ipt,采用清醒无创心功能血流动力学实验方法 ,观察Ipt对对心功能和血流动力学的影响。结果 :在RHD模型上 ,单次口服Ipt0 .1 2 5、0 .2 5、0 .5、1 .0mg·kg- 1 后 ,产生剂量依赖性的降压作用 ,0 .5h开始起效 ,2～ 3h达效应峰值 ,其最大降低SBP幅度分别为 1 3、2 3、2 5、3 6mmHg,降压作用维持时间分别为 4、6、6、1 2h。在清醒正常血压犬上 ,单次口服Ipt 0 .8,3 .2 ,1 2 .8mg·kg- 1 ,其中剂量为 0 .8和 3 .2mg·kg- 1 时 ,血压和心率均无明显变化 ,剂量增至 1 2 .8mg·kg- 1 时 ,在给药后 5h之内可以显著降低收缩压和舒张压 ,其最大降低SB     

糖尿病合并高血压的降压治疗

目的探讨糖尿病合并高血压的降压治疗效果。方法将Ⅱ型糖尿病合并高血压患者23例随机分为A组8例、B组7例、C组8例。A组予硝苯地平缓释片;B组采用硝苯地平和缬沙坦联合给药方案;C组采用硝苯地平+吲哒帕胺联合方案。观察对比3组患者治疗前后的血压变化情况及不良反应。结果 3组患者在降压治疗后,其舒张压和收缩压均有显著下降(P<0.01)。其中,B组舒张压下降幅度最大,与其他2组比较差异有统计学意义(P<0.01);C组收缩压下降幅度最大,明显大于另外2组(P<0.01)。A组患者血压达标比率明显低于另外2组(P<0.01)。A组不良反应发生率高于B、C组,差异均有统计学意义(P<0.05)。结论硝苯地平联合血管紧张素转换酶抑制剂或利尿剂能取得较为满意的降压效果,且不良反应少。     

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。     

Hypotensive effect of nifedipine in hypertensive patients with chronic renal failure

The hypotensive effect of 4-(2'-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxydimethylester (nifedipine, Adalat) was studied in 15 hypertensive patients with chronic renal failure. The decrease of blood pressure lasted for approximately 3 h and maximum decrement was achieved in 1 h after oral administration of nifedipine (10 mg). Hypotensive action of the drug was associated with a constant decrease in total peripheral resistance and an increase in cardiac output, plasma renin activity (PRA), and plasma norepinephrine (noradrenaline). Initial PRA was apparently the major determinant of the rise in PRA since a close correlation was present between the initial value and the increase induced by nifedipine (r = 0.93, p less than 0.05). Marked reduction of blood pressure without noticeable side effects was observed in two cases who had not responded to previous antihypertensive treatment. These data suggest that nifedipine exerts its hypotensive action through peripheral vasodilation and may be an effective drug for treatment of hypertension during chronic renal failure.     

Cardiovascular responses to verapamil and nifedipine in hypoventilated and hyperventilated rats.

1. The influence of hypoventilation or hyperventilation on blood pressure and pulse rate responses to verapamil and nifedipine was studied in chloralose-anaesthetized rats. 2. Artificial ventilation with room air at a fixed volume of 10 ml kg-1 successfully induced combinations of hypoxaemia, hypercarbia and acidosis at a ventilator rate of 37 strokes min-1 and of hyperoxaemia, hypocarbia and alkalosis at 160 strokes min-1. 3. Hypoventilation caused significant decreases in both the blood pressure and pulse rate, whereas hyperventilation produced significant increases in these parameters. 4. In the controls, intravenous injections of graded doses of either verapamil or nifedipine caused dose-dependent decreases in mean blood pressure. The effects on pulse rate were not marked. 5. The hypotensive effects of verapamil were significantly more intense in hyperventilated rats, whereas those of nifedipine were significantly less pronounced in hypoventilated animals. The hypoventilated rats exhibited a significant dose-dependent decrease in pulse rate in response to verapamil administration. 6. It is concluded that cardiovascular responses to verapamil, nifedipine and probably other calcium antagonists are altered in the presence of blood gas abnormalities.     

CARDIOVASCULAR RESPONSES TO NIFEDIPINE IN ANAESTHETIZED RATS WITH ABNORMAL BLOOD GAS/PH LEVELS

1. Blood pressure and pulse rate responses to intravenously (i.v.) administered nifedipine were studied in chloralose-anaesthetized rats subjected to hypoxaemia, hyperoxaemia, alkalosis, acidosis, hypocarbia with alkalosis, or hypercarbia with acidosis. 2. Ventilation with a gas mixture of 17% O2, 28% O2, or 23% O2 with 5% CO2 at a fixed stroke volume (10 mL/kg) and rate (80 strokes/min) induced hypoxaemia, hyperoxaemia or hypercarbia, respectively. Hypocarbia was induced by ventilation with 17% O2 at 160 strokes/min. Acidosis or alkalosis was produced by intravenous infusion of 1 mol/L HCl or 1 mol/L NaHCO3, respectively, in animals ventilated with room air. 3. There were significant decreases in blood pressure and pulse rate during acidosis, and increases in pulse rate during alkalosis and hypercarbia. No marked changes in these parameters were observed under the other experimental conditions. 4. The control animals showed a dose-dependent decrease in blood pressure without marked changes in pulse rate in response to nifedipine injection. 5. Significant reductions in the hypotensive effect of nifedipine were observed in rats subjected to alkalosis, acidosis, or hypercarbia. A similar tendency was also found during hypocarbia while the responses to nifedipine during hypoxaemia and hyperoxaemia were statistically the same as those in the controls. 6. It is concluded that alterations of blood pH reduce the hypotensive effect of nifedipine, and we suggest that blood pH changes probably play a more important role than PO2 or PCO2 abnormalities in altering the cardiovascular responses to nifedipine in hypoventilated or hyperventilated rats.     

Antihypertensive effect of a new dihydropyridine calcium entry blocker in conscious hypertensive and normotensive rats

The antihypertensive effects of orally administered CD-349, (2-nitratopropyl-3-nitratopropyl-2,6-dimethyl-4-(3-nitrophen yl)- 1,4-dihydropyridine-3,5-dicarboxylate), a new dihydropyridine calcium-entry blocker, were evaluated in comparison with nifedipine in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR) and normotensive rats (NTR) all in a conscious state. CD-349 (0.3, 1.0 and 3.0 mg/kg) and nifedipine (1.0 mg/kg) produced a long-lasting decrease in mean arterial blood pressure (BP) and an increase in heart rate (HR) in all the rat groups; the effects of CD-349 were dose-dependent and greater in hypertensive rats than in NTR. As compared with nifedipine at the same dose of 1 mg/kg, the hypotensive effect of CD-349 was relatively slower in onset and longer-lasting, thereby suggesting that gastrointestinal absorption of CD-349 was slower than that of nifedipine. The increase in HR associated with the hypotension induced by CD-349 at 1 mg/kg was relatively transient in comparison with that induced by nifedipine at the same dose in both types of hypertensive rat. From these results, it is expected that CD-349 could be a useful antihypertensive drug.     

Cardiovascular effects of the essential oil of Alpinia zerumbet leaves and its main constituent,Terpinen-4-ol,in rats: role of the autonomic nervous system

Cardiovascular effects of intravenous ( i. v.) treatment with the essential oil of Alpinia zerumbet (EOAZ) were investigated in rats. Additionally this study examined (I) whether the autonomic nervous system is involved in the mediation of EOAZ-induced changes in mean aortic pressure (MAP) and heart rate (HR), and (II) whether these changes could be, at least in part, attributed to the actions of terpinen-4-ol (Trp-4-ol), the major constituent of EOAZ. In both pentobarbitone-anaesthetised and conscious rats, i. v. bolus injections of EOAZ (1 to 20 mg/kg) elicited immediate and dose-dependent decreases in MAP. In anaesthetised rats, EOAZ decreased HR only at higher doses (10 and 20 mg/kg), while changes of this parameter were not uniform in conscious rats. Hypotensive responses to EOAZ were of the same order of magnitude or duration, irrespective of whether the animal was under general anaesthesia. Pretreatment of anaesthetised rats with bilateral vagotomy did not modify significantly the hypotensive and bradycardic responses to EOAZ. In conscious rats, i. v. injections of bolus doses (1 to 10 mg/kg) of Trp-4-ol also elicited immediate and dose-dependent decreases in MAP. However, these hypotensive effects were significantly greater than those evoked by the same doses of EOAZ (1 to 10 mg/kg). Intravenous pretreatment of conscious rats with either methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) had no significant effects on the EOAZ-induced hypotension. These data show that i. v. treatment with the EOAZ in either anaesthetised or conscious rats induced an immediate and significant hypotension, an effect that could be partially attributed to the actions of Trp-4-ol. The hypotension appears independent of the presence of an operational sympathetic nervous system, suggesting that the EOAZ may be a direct vasorelaxant agent.     

Haemodynamic effects of combined oral nifedipine and sublingual nitroglycerin in patients with chronic stable angina

Summary We examined the pharmacokinetics of nifedipine after acute and sustained oral therapy and the potential haemodynamic interaction between nifedipine and sublingual nitroglycerin in nine patients with chronic stable angina.Nifedipine pharmacokinetics after a single oral dose and sustained dosing (three times daily for five days) were not significantly different. Single dose nifedipine produced a statistically significant decrease in standing and supine systolic and diastolic blood pressures when compared to placebo. A significant decrease in the supine systolic pressure was observed after sustained nifedipine therapy. Except for this change, other hypotensive effects of nifedipine after sustained therapy were not different to those of placebo, in spite of persistent plasma nifedipine concentrations after repeated dosing.There were no observable correlations between nifedipine haemodynamics and pharmacokinetics in these patients, nor were there any significant haemodynamic interactions between sublingual nitroglycerin with either acute or sustained nifedipine treatment.The transient haemodynamic effects of sublingual nitroglycerin were not potentiated by either acute or sustained nifedipine therapy.     

Antihypertensive effects of nisoldipine and reference drugs in certain types of hypertensive rats

The hypotensive effects of nisoldipine (Bay K 5552), compared with those of nifedipine, nicardipine and hydralazine, in normotensive rats (NR), spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DNR) and renal hypertensive rats (RHR), were studied. The changes in plasma renin activity (PRA) after treatment with nisoldipine and these reference drugs were also studied. The results of this study revealed that: 1. Nisoldipine caused more potent antihypertensive effects in SHR, DNR and RHR than in NR. 2. The antihypertensive effects of nisoldipine in SHR were almost equipotent to those of nifedipine, nicardipine and hydralazine. However, in NR, DNR and RHR, the effects of nisoldipine were weaker than those of the reference drugs. 3. The positive chronotropic effects of nisoldipine were less remarkable than those elicited by nifedipine, nicardipine and hydralazine in all types of hypertensive rats, except SHR. 4. As did nifedipine and nicardipine, nisoldipine caused an increase of the plasma renin activity in NR and SHR, though its potency was weaker than those of nifedipine and nicardipine.     

Acute hypotensive, natriuretic, and hormonal effects of nifedipine in salt-sensitive and salt-resistant black normotensive and hypertensive subjects.

In a randomized double-blind study, we compared the short-term effects of nifedipine (10 mg 3x daily for 1 day) versus placebo on 24-h blood pressure, diuresis, natriuresis, urinary excretion of dopamine and metabolites, and on plasma renin activity (PRA) and plasma aldosterone levels in 18 black hypertensive (HT) patients [eight salt-resistant (HT-SR) and 10 salt-sensitive (HT-SS)], and in 20 black normotensive (NT) subjects (12 NT-SR and eight NT-SS) who were studied randomly with both a high- (HS) and a low-salt (LS) diet. In comparison to placebo, nifedipine significantly decreased 24-h mean BP in all groups either with HS or LS diets (all p<0.05). With HS, greater hypotensive effects were achieved in NT-SS (-10+/-2 mm Hg) versus NT-SR (-3+/-1 mm Hg; p<0.05) and in HT-SS (-18+/-2 mm Hg) versus HT-SR (-12+/-2 mm Hg; p<0.05). In NT-SS and HT-SS, nifedipine induced greater (p<0.05) BP decrease with HS (-10+/-2 and -18+/-2 mm Hg) than with LS (-4+/-1 and -9+/-1 mm Hg, respectively), whereas in NT-SR and HT-SR, the hypotensive effect did not differ between HS and LS. Nifedipine versus placebo significantly increased natriuresis and fractional excretion of sodium in all groups only with HS (p<0.05) but not with LS diets. Only in HT-SS were the hypotensive and natriuretic effects of nifedipine significantly correlated (r = -0.77; p<0.01). Nifedipine produced a similar increase of the urinary excretion of dopamine, L-DOPA, and of DOPAC in all subjects, which did not correlate with hypotensive and natriuretic effects. Nifedipine did not modify plasma levels of renin and of aldosterone except in NT-SS with HS, in whom nifedipine increased PRA levels (p <0.05). We conclude that although nifedipine reduces BP in all groups of NT and HT with LS and HS diets, the effect is greater in salt-sensitive subjects with HS. Although in HT-SS with HS, the short-term natriuretic response to nifedipine may contribute to its hypotensive effects, the diuretic-natriuretic effect of nifedipine is not necessary for the expression of its hypotensive effect. Moreover, it is unlikely that any short-term effects of nifedipine either on the renal dopaminergic system or on the secretion of aldosterone explain nifedipine short-term hypotensive and diuretic-natriuretic effects.     

Interaction of dl-mandelamidine (Olimidine) with some antihypertensive drugs expressed in the blood pressure of conscious rats]

Hypotensive effect of dl-Mandelamidine (Olmidine, MA) in combination with some established antihypertensive drugs was studied in conscious normotensive rats. The mean blood pressure and heart rate were measured by means of a pressure transducer via a polyethylene tube inserted into the abdominal aorta of rat according to the method described by Weeks. The results obtained were as follows; 1) The hypotensive effects of guanethidine and hydrochlorothiazide were enhanced in combination with MA. 2) The hypotensive effect of reserpine was reduced by MA. 3) The hypotensive effects of clonidine, C6, propranolol and hydralazine were uneffected by MA. On the other hand, changes in heart rate induced by reserpine and C6 were increased by MA, however, those induced by guanethidine, clonidine propranolol and hydralazine were decreased by MA. The slight decrease in heart rate induced by hydrochlorothiazide was uneffected by MA. In view of our data, it is considered important that investigation of the interaction of antihypertensive drugs be done using conscious animals, as these drugs will be clinically prescribed.     

缓释型硝苯地平与氨氯地平的降压作用比较

目的：比较缓释型硝苯地平与氨氯地平的动态降压作用。方法：１７例中、轻度原发性高血压病人（男性８例，女性９例，年龄４３±ｓ６ａ）８例予缓释型硝苯地平２０ｍｇ，ｐｏ，ｑｄ，９例予氨氯地平５～１０ｍｇ，ｐｏ，ｑｄ，×４ｗｋ。服药前、后做２４ｈ动态血压测定及踏车运动激发试验（ｎ＝１６）。结果：２药均有效地降低２４ｈ平均血压，但降压谷／峰（Ｔ／Ｐ）比值，收缩压（ＳＢＰ）Ｔ／Ｐ比值缓释硝苯地平组高于氨氯地平组，分别为８７％与７４％；舒张压（ＤＢＰ）Ｔ／Ｐ比值氨氯地平组高于缓释硝苯地平组，分别为８１％与６２％；运动激发下，服氨氯地平后ＤＢＰ仍能显著下降（Ｐ＜０．０１）及心率减慢（Ｐ＜０．０５）。结论：氨氯地平降２４ｈＤＢＰ的平稳性及对运动的耐受性均较缓释硝苯地平好。