尼群地平与氨酰心安单用及合用治疗高血压病的降压效果和对左心功能…

高血压病Ｉ，Ⅱ期９０例分为三组，对尼群地平２０ｍｇ，氨酰心安５０ｍｇ单用及合用而剂量减半的降压效果和左心功能影响进行了比较，结果表明两药合用副作用减少，降压效果不变，对左室收缩和舒张功能改善更加全面。     

钩藤碱、钩藤总碱合用双肼苯哒嗪对清醒动物降压效应的研究

钩藤碱６０ｍｇ·ｋｇ－１合用双肼苯哒嗪３ｍｇ·ｋｇ－１十二指肠给药，１ｈ时降低清醒大鼠血压２３％，降低高血压模型大鼠血压２８％，降压幅度超过一药单用及等剂量钩藤总碱与双肼苯哒嗪合用的幅度，合并用药可克服单用后药的加快心率作用。双肼苯哒嗪０．８ｍｇ·ｋｇ－１ｉｖ加快心率，增加分钟心肌张力—时间指数，合用钩藤碱１５ｍｇ·ｋｇ－１增强了前药的降压效果，而心率、分钟心肌张力—时间指数未见明显变化。     

尼群地平、依那普利与牛磺酸合并应用对肾性高血压大鼠降压的协同研究

尼群地平１０ｍｇ·ｋｇ－１、依那普利１０ｍｇ·ｋｇ－１和牛磺酸５０ｍｇ·ｋｇ－１一次口服对肾性高血压大鼠均有降压作用，三者降压作用强度相当，最大降压百分率（给药后６ｈ）分别为３３、３６．６和２５．１，降压持续时间相似，给药后２４ｈ的降压百分率分别为１４．２、４．８和１３．７。尼群地平，依那普利分别与牛磺酸以及尼群地平与依那普利合用均有协同降压作用，Ｑ值分别为２．２１、２．６７和１．６４，且降压作用持久，给药后２４ｈ的降压百分率分别为３９．６、２６．８和３８．８，显著高于各药单用。     

钩藤碱,钩藤总碱合用双肼七苯哒嗪地清桓动物降压效应的研究

钩藤碱６０ｍｇ．ｋｇ＾－１合用双肼苯哒嗪３ｍｇ．ｋｇ＾－１十二指肠给药，１ｈ时降低清桓大鼠血压２３％，降低高血压模型大鼠血压２８％，降压芳超过一药单用及等剂量钩藤总碱与双肼苯哒嗪合用的幅度，合并用药可克服单用后药的加快心率作用。双肼苯哒嗪０．８ｍｇ．ｋｇ＾－１ｌｖ加快心率，增国分钟心肌张力－时间旨数，合用钩藤碱１５ｍｇ．ｋｇ＾－１增强了前药的降太效果，而心率分钟心肌张力－时间指数未见明显变化。     

依那普利和牛磺酸逆转肾性高血压大鼠左心室肥厚及抗心律失常的作用

肾性高血压大鼠形成左心室肥厚后，心肌线粒体Ｃａ２＋含量和用成串电脉冲刺激离体心脏引起的心律失常发生率显著增高。依那普刊（６ｍｇ·ｋｇ－１），牛磺酸（３０ｍｇ·ｋｇ－１）在左心室肥厚形成后（术后第９周）开始连续ｐｏ给药９周，均能显著降低血压、左心室重与体重的比值、电刺激引起的心律失常发生率和心肌线粒体Ｃａ２＋含量，且两药合用后，降压作用增强，本实验表明，肾性高血压左心室肥厚大鼠的心脏对电刺激的敏感性增加．更容易产生心律失常；依那普利和牛磺酸对肾性高血压大鼠有降压、逆转左心室肥厚的作用，并能降低左心室肥厚大鼠的心脏对电刺激的敏感性。     

尼群地平,依那普利与牛磺酸合并应用对肾性高血压大鼠降压的…

尼群地平１０ｍｇ．ｋｇ＾－１、依那普利１０ｍｇ．ｋｇ＾－１和牛磺酸５０ｍｇ．ｋｇ＾－１一次口对肾性高血压大鼠均有降压作用，三者降压作用强度相当，最大降压百分率持续时间相似，给药后２４ｈ的降压百分率分别为１４．２、４．８和１３．７。尼群地平，依那普利分别与牛磺酸以及尼群地平与依那普利全用均有协同降压作用，Ｑ值分别为２．２１、２．６７和１．６４，且降压作用持久，给药后２４ｈ的降压百分率分别为３９．６、     

降压药物的相互作用

为了增强降压药的治疗效果,扩大适应症,减少副作用,临床上往往不单纯加大某药的单一用药量,而采用两种或两种以上药物合用的方法。尤其高血压常合并心脏病为主要的其它疾病,更需与其它药物合用。于是就产生了降压药之间以及降压药与其它治疗药合用时的相互作用问题。一、降压药物合用时的相互作用降压药物合用恰当与否及其降压效果如何,见下表: (一)利尿剂不能与利尿剂合用的降压药基本上没有,但从病人的日常活动或工作考虑,用利尿剂恰当与否,还值得研究。ACE抑制剂可改善劳动能力,甲基多巴使其     

卡维地洛与非洛地平缓释片治疗难治性肾性高血压的疗效及安全性评价

目的观察卡维地洛和非洛地平缓释片（波依定）对慢性肾功能不全（氮质血症期）伴难治性高血压的降压效果及安全性评价。方法82例肾功能不全合并高血压患者被随机分成2组，观察组45例服用卡维地洛和非洛地平缓释片，对照组37例服用非洛地平缓释片，比较治疗8周后2组降压效果、白细胞、电解质、肾功能、血糖、血脂变化。结果服药8周后观察组降压总有效率为93．33％，对照组总有效率78．38％，2组比较差异有统计学意义。结论卡维地洛与非洛地平缓释片2药合用能显著提高对难治性肾性高血压的降压疗效且降压平稳、使用安全。     

氯沙坦治疗高血压的临床应用

目的 探讨氯沙坦在临床上的降压效果.方法 利用分组对照方法,了解氯沙坦及氯沙坦与其它药合用治疗高血压的疗效.结果 口服氯沙坦后能够稳定地降低血压,还能有效地控制患者清晨高峰期血压,与利尿药合用,降压效果更显著.与螺内酯合用可以延缓急性心肌梗死后的心室重构过程,有效地抑制心肌梗死后的心肌纤维化过程.结论 氯沙坦治疗高血压有确切的疗效,而且不良反应轻微、病人耐受性好、无咳嗽现象发生.     

牛磺酸与硫酸镁联合用药的研究──Ⅰ、抗实验性缺血／再灌心律失常作用

采用麻醉大鼠缺血／再灌心律失常模型，研究牛磺酸（Ｔａｕｒ）和硫酸镁（ＭｇＳＯ４）单用及合用的抗再灌心律失常作用，并观察对正常大鼠在体血流动力学的影响。结果表明：Ｔａｕｒ５０ｍｇ·ｋｇ－１，ＭｇＳＯ４２５ｍｇ·ｋｇ－１具有部分抗心律失常作用；Ｔａｕｒ１００、１５０ｍｇ·ｋｇ－１，ＭｇＳＯ４５０、１００ｍｇ·ｋｇ－１抗心律失常疗效增加；两药小剂量合用，作用较各单用药组明显增强。ＭｇＳＯ４２５ｍｇ·ｋｇ－１对大鼠心肌仅有轻度负性肌力作用，与Ｔａｕｒ５０ｍｇ·ｋｇ－１合用，负性肌力未见增加，但具有负性频率和减低心肌耗氧量作用，提示其抗心律失常作用与保护心肌有一定关系。     

缬沙坦治疗高血压病合并舒张性心功能不全116例

目的:探讨缬沙坦对血管紧张肽转换酶抑制药不能耐受的高血压合并舒张性心力衰竭(心衰)病人心功能的影响。方法:116例高血压合并左室扩大舒张性心衰病人随机分为治疗组61例,对照组55例,均给予硝酸异山梨醇酯10mg,po,tid,阿司匹林100mg,po,qd;治疗组加服缬沙坦80～160mg, po,qd,对照组加服尼群地平10～20mg,po,tid,疗程均为6mo。采用超声心动图进行对比观察。结果:治疗组反映左室形态的指标(LVID和LVMW)及反映左室舒张功能指标(E峰,A峰,E/A比值, VTIE,VTIA,E-VTI/A-VTI)有明显改善(P<0.05),与对照组比较差异显著(P<0.05)。临床疗效评定,治疗组及对照组总有效率分别为87％和54％,死亡率分别为2％和9％,2组比较有非常显著差异(p<0.01)。结论:缬沙坦不仅可改善左室舒张功能,逆转扩大的左心室,并明显降低死亡率。     

Effect of antihypertensive treatment with nitrendipine on left ventricular mass and diastolic filling in patients with mild to moderate hypertension.

Nitrendipine is a dihydropyridine calcium antagonist that may be active when administered once daily. The aim of the study was to assess the effect of antihypertensive treatment with nitrendipine (20-40 mg) on left ventricular mass and diastolic function. Forty patients with mild to moderate hypertension (diastolic pressure greater than or equal to 90 and less than or equal to 114 mm Hg) were enrolled; a complete echo Doppler examination was performed at baseline, and 8 and 12 months after treatment in order to measure left ventricular mass and diastolic and systolic function. Only 28 patients completed the study follow-up. At month 8 nitrendipine had already successfully reduced blood pressure (mean 122 +/- 9 to 92 +/- 10 mm Hg) without modifying heart rate, and left ventricular mass index (150 +/- 48 to 123 +/- 34 g/m2), with a further reduction at month 12. Isovolumic relaxation time was reduced at month 8 from 138 +/- 28 to 111 +/- 17 ms, but the diastolic pattern was completely modified only after 1 year, with a normalization of deceleration time (from 220 +/- 35 to 188 +/- 12). Systolic function did not change. Our results indicate that nitrendipine is a powerful antihypertensive agent that reduces left ventricular mass, but requires a longer period of time to improve diastolic filling pattern.     

血压波动性在尼群地平和阿替洛尔联合治疗自发性高血压大鼠的器官保护中的重要性

AIM: To study the importance of reduction of blood pressure variability (BPV) in the organ protection of long-term treatment with combination of nitrendipine and atenolol, which was abbreviated as Nile, in spontaneously hypertensive rats (SHR). METHODS: Combination of nitrendipine (10 mg/kg/d) and atenolol (20 mg/kg/d) was given in SHR chow for 12 weeks. Blood pressure (BP) was then recorded during 24 h in conscious state. After the determination of baroreflex sensitivity (BRS), rats were killed for organ-damage evaluation. RESULTS: Long-term treatment with Nile significantly decreased BP and BPV, ameliorated impaired BRS, and obviously diminished end-organ damage in SHR. The indices of left ventricular and aortic hypertrophy, and glomerulosclerosis score were all positively related to BP and BPV, and negatively related to BRS in untreated and Nile-treated SHR. Multiple-regression analysis showed that decrease in left ventricular and aortic hypertrophy was mainly related to the decrease in systolic BPV, and amelioration in renal lesion was mainly determined by increase in BRS. CONCLUSION: Long-term treatment with Nile possessed obvious organ protection in SHR. Besides the BP reduction, the decrease in BPV and the restoration of BRS may importantly contribute to this organ protection.     

缬沙坦联合依那普利治疗充血性心力衰竭的临床研究

目的探讨依那普利、缬沙坦二者联合治疗对充血性心力衰竭(CHF)的疗效及其对肾素、血管紧张素及醛固酮系统(RAAS)的影响。方法将48例心力衰竭患者按照纽约心脏病协会分级(NYHA-FC)心功能Ⅱ~Ⅳ级,随机分为对照组(22例),予依那普利5mg,每日2次;治疗组(26例),予缬沙坦80mg,每日1次和依那普利5mg,每日2次;治疗约4个月;观察治疗前后的左室功能、血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)及醛固酮(ALD)水平的变化。结果两组病人治疗后心功能(NYHA分级)均有改善;两组治疗前后相比,左室射血分数(LVEF)值均显著提高(P<0.01),左室舒张末期内径(LVIDd)缩短(P<0.01);治疗组较对照组LVEF,LVIDd改善更显著;对照组治疗后PRA、AngⅡ、ALD水平无变化,治疗组AngⅡ水平升高(P<0.05),ALD水平降低(P<0.01);两组患者治疗后血尿素氮、肌酐水平均无显著变化。结论缬沙坦和依那普利联合治疗无论从改善左室功能及抑制左室重构均优于单独用药。     

尼群地平、卡托普利对充血性心力衰竭患者血清地高辛浓度的影响及其疗效比较

２２例心力衰竭患者随机分为尼群地平组１２例和卡托普利组１０例，服地高辛０．２５ｍｇ，ｑｄ，１０ｄ后，合用尼群地平（１０ｍｇ，ｐｏ，ｂｉｄ）或卡托普利（２５ｍｇ，ｐｏ，ｔｉｄ）１４ｄ，合用药前后取血、留尿，放射免疫法测定其中地高辛浓度并作心功能检查。结果：卡托普利使血清地高辛浓度（ＳＤＣ）降低１９％（Ｐ＜０．０５）、肾地高辛清除率（Ｃｌｄｉｇ）增加３５％（Ｐ＜０．０１），而尼群地平对它们无明显影响，但显著改善心功能，疗效不比卡托普利差。     

A comparison of the haemodynamic effects of nifedipine,nisoldipine and nitrendipine in man

Summary Nifedipine (10 mg), nisoldipine (10 mg) and nitrendipine (20 mg) were given orally to 8 normal volunteers in a placebo controlled, double blind, crossover study.Blood pressure (BP), pulse (P) and systolic time intervals (STI) were recorded at time 0, 30, 60, 90, 120 min after drug administration. Adverse effects were also recorded.There was a fall in BP, pre-ejection time (PEP), PEP/LVET (left ventricular ejection time) and electro-mechanical systole index (QS2 index), and a rise in LVET index in response to the three active drugs compared with placebo.All active drugs, but not placebo, were associated with adverse effects.     

非洛地平加吲哒帕胺与加利尿药对高血压左室肥厚及心功能影响比较

目的 :比较非洛地平联用吲哒帕胺与非洛地平联用利尿药治疗老年中、重度高血压的疗效和对左室肥厚 (LVH )、左室舒张功能的影响。方法 :6 0例高血压伴左室肥厚病人随机分为 2组 ,停用降压药 1wk。一组非洛地平 5mg联用吲哒帕胺 2 .5mg ,po ,qd× 4 8wk ,另一组非洛地平 5mg联用氢氯噻嗪 2 5mg ,po ,qd× 4 8wk。结果 :非洛地平联用氢氯噻嗪组和联用吲哒帕胺组降压总有效率分别为90 % ,83% (P >0 .0 5)。 2组均可明显改善LVH及左室舒张功能 ,(P <0 .0 1)。但非洛地平联用吲哒帕胺组改善更显著 ,组间比较 ,P <0 .0 1。不良反应小 ,不影响糖、脂肪代谢。结论 :对老年中、重度高血压 ,非洛地平联用吲哒帕胺是一组适合长程治疗的满意组合     

Beneficial effects of the combination of nifedipine and losartan in hypertensive Dahl salt-sensitive rats

BACKGROUND: The antihypertensive and organ-protective effects of the combination of the angiotensin II type 1 receptor blocker losartan and the calcium channel blocker nifedipine were examined in Dahl salt-sensitive rats. METHODS: The rats fed with a high-salt diet developed hypertension accompanied by aorta and heart hypertrophy, and impaired renal function. The animals were treated with losartan (30 mg/kg/day), nifedipine (7.8 mg/kg/day) or with a combination of both drugs for 8 weeks. At the end of the study systolic blood pressure, kidney function, organ weight, and mRNA expression were investigated. RESULTS: Losartan reduced significantly the systolic blood pressure as well as the aorta and left ventricular hypertrophy. Nifedipine and its combination with losartan had similar effects on the systolic blood pressure, aorta and left ventricular hypertrophy but only the combination treatment reduced the expression of transforming growth factor-beta1 in aorta and brain natriuretic peptide in left ventricle significantly. Nifedipine and the combination therapy reduced proteinuria and improved urine creatinine excretion. The expression of collagen III and IV in the kidney was significantly reduced by the combination therapy. CONCLUSION: These results indicate that although losartan and nifedipine were effective in lowering blood pressure and showed moderate organ protection, additional benefits can be expected by combination therapy with both compounds.     

Effects of nitrendipine and cilazapril alone or in combination on hemodynamics and regional blood flows in conscious spontaneously hypertensive rats

Nitrendipine and cilazapril are two new antihypertensive drugs with different mechanisms of action. Nitrendipine is a calcium antagonist of the dihydropyridine class which decreases directly the smooth muscle tone. Cilazapril is a new long-lasting inhibitor of angiotensin-converting enzyme which suppresses the peripheral vasoconstrictor effect of angiotensin I by inhibiting its transformation in angiotensin II. The goal of the present study was to assess the effects on hemodynamics and regional blood flows (measured with radioactive microspheres) of cilazapril and nitrendipine given alone or in combination. Cilazapril (3 mg/kg) and nitrendipine (0.3 mg/kg) were given intravenously to conscious spontaneously hypertensive rats first alone, then in combination. Both cilazapril and nitrendipine decreased mean arterial pressure to the same extent. Cilazapril increased regional blood flow only in the kidney without changing total cardiac output. In contrast, nitrendipine increased regional blood flow in nearly every organ and markedly enhanced total cardiac output. Cilazapril redistributed the cardiac output distribution toward the kidney, and nitrendipine did not change the cardiac output distribution. The combination of both nitrendipine and cilazapril produced a stronger antihypertensive effect than each drug alone. The peripheral vasodilatation with the combination was not as marked as with nitrendipine alone but was associated with the same redistribution of the cardiac output toward the kidney as with cilazapril. We conclude that after acute intravenous administration the combination of cilazapril and nitrendipine produced hemodynamic effects which cannot be induced by each drug used alone. Such a therapeutic profile may be useful in patients with high blood pressure or heart failure.     

Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension

The fixed-dose combination of enalapril 10mg with nitrendipine 20mg combines an ACE inhibitor with a calcium channel antagonist (CCA) and is indicated for the treatment of patients with mild-to-moderate hypertension whose blood pressure (BP) is inadequately controlled with enalapril or nitrendipine monotherapy. In randomised, double-blind clinical trials, enalapril/nitrendipine 10/20 mg/day was significantly more effective than its individual components in reducing diastolic BP (DBP) in patients with mild-to-moderate hypertension inadequately controlled with enalapril 10 mg/day or nitrendipine 20 mg/day. The fixed-dose combination was similar in efficacy at reducing DBP to amlodipine 10 mg/day in patients who failed to achieve BP control with amlodipine 5 mg/day, and to losartan/hydrochlorothiazide 50/12.5 mg/day in patients who received the combinations as first-line therapy. Enalapril/nitrendipine 10/20 mg produced a consistent antihypertensive effect that persisted for the entire 24-hour dosage interval as shown by ambulatory BP monitoring. Enalapril/nitrendipine 10/20 mg was well tolerated in clinical trials where it was administered to patients with mild-to-moderate hypertension for up to 12 weeks. The adverse events were those expected of ACE inhibitors and CCAs and included cough, headache and flushing. Evidence from clinical trials, including a pooled analysis, suggests that the incidence of oedema may be significantly lower with the fixed-dose combination than with CCA monotherapy.In conclusion, enalapril/nitrendipine 10/20 mg is a well tolerated fixed-dose combination of two established antihypertensive agents administered once daily that effectively lowers BP throughout the 24-hour dosage interval. Importantly, the fixed-dose combination may have a lower incidence of oedema than CCA monotherapy. Enalapril/nitrendipine 10/20 mg provides an additional treatment option for patients with mild-to-moderate hypertension for whom combination therapy is appropriate.