Effects of the combination of low-dose nifedipine GITS 20 mg and losartan 50 mg in patients with mild to moderate hypertension

Most hypertensive patients require more than one medication to effectively control elevated blood pressure (BP) values. This multicenter, randomized, double-blind study was aimed at testing the efficacy and safety of the combination of low-dose nifedipine GITS 20 mg/ losartan 50 mg compared with either monotherapy in patients with grade 1 to 3 hypertension over an eight-week period. Of 352 patients enrolled in the study, 300 were randomized. All the three treatments lowered elevated BP without clinically relevant changes in heart rate. All the three treatments lowered mean 24-hour diastolic BP: nifedipine GITS/losartan -10.6 mm Hg, losartan -5.4 mm Hg, nifedipine GITS 20 mg -8.0 mm Hg. There was a statistically significant difference of diastolic BP change between patients receiving losartan compared with those receiving combination treatment (P < 0.05). Diastolic BP trough-to-peak ratio and smoothness index were highest in the patient group receiving combination therapy (70%). Nifedipine GITS monotherapy had the highest systolic BP trough-to-peak ratio of all treatment arms (78%) and higher diastolic BP trough-to-peak ratio and smoothness index than losartan monotherapy. All treatments were safe. These data provide evidence that in hypertensive patients combination of nifedipine GITS 20 mg and losartan 50 mg improves control of systolic and diastolic BP compared with either monotherapy.     

N(G)-nitro-L-arginine methyl ester-induced hypertension and natriuretic peptide gene expression: inhibition by angiotensin II type 1 receptor antagonism

This study examined the role of angiotensin II in the increase of blood pressure, activation of cardiac natriuretic peptide gene expression, left ventricular hypertrophy, and vascular changes in nitric oxide-deficient hypertension. N(G)-nitro->L-arginine methyl ester (>L-NAME, 20 mg/kg/d), angiotensin II type 1 receptor (AT ) antagonist losartan (20 mg/kg/d), or their combination were administered orally for 8 weeks in Wistar rats. >L-NAME elevated systolic blood pressure, which reached its maximum within 4 weeks (200 +/- 4 mm Hg). Despite hypertension, >L-NAME administration for 8 weeks did not induce left ventricular hypertrophy. Losartan treatment significantly decreased the development of hypertension induced by >L-NAME and decreased left ventricular hypertrophy in untreated rats. In contrast, losartan did not prevent the hypertrophic remodeling of the mesenteric resistance arteries induced by >L-NAME. >L-NAME treatment increased ventricular atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels and immunoreactive BNP levels significantly. Losartan therapy decreased the >l-NAME-induced ventricular ANP gene expression by 69% (p < 0.05) and also reduced ventricular BNP mRNA levels so that it did not differ from control. Losartan treatment alone decreased ventricular immunoreactive ANP and BNP levels by 30% (p < 0.05). These results show that ventricular ANP and BNP gene expression are dissociated from the increased ventricular mass in nitric oxide deficiency-induced hypertension. Results suggest that >l-NAME-induced hypertension and the associated activation of ventricular ANP and BNP gene expression are, at least in part, mediated by angiotensin II, whereas the resistance vessel hypertrophy following nitric oxide synthase inhibition is angiotensin II independent.     

氯沙坦逆转自发性高血压大鼠心血管肥厚作用的研究

目的：探讨氯沙坦逆转心血管肥厚的作用与心血管局部组织中内皮素（ET）的关系。方法：16周龄的自发性高血压大鼠（SHR）随机分成氯沙坦治疗组（SHR－L）与对照组（SHR－C）。另设同源正常血压大鼠（WKY）组，饲养共6周。大鼠的收缩压和心率用尾套法测量，左室重量指数（LVI）及主动脉中膜与内径比率测微计测量，血浆，心肌和主动脉含量用放免法测定，以SHR－C组做直线相关分析。结果：氯沙坦能显著降低SHR的收缩压，SHR－L与SHR－C组比较LVI及主动脉中膜内内径比值下降，左室及主动脉ET，SHR－C组高于WKY组，且分别与LVI及主动脉中膜和内径比值呈正相关。结论：左室及主动脉组织中ET升高是造成左室及主动脉肥厚的重要因素，氯沙坦通过阻断受体和降低血浆及血管组织中的含量产生降压及逆转心血管肥厚的作用。     

Benazepril combined with either amlodipine or hydrochlorothiazide is more effective than monotherapy for blood pressure control and prevention of end-organ injury in hypertensive Dahl rats

We studied the effect of hydrochlorothiazide (HCTZ), the angiotensin-converting enzyme inhibitor benazepril, the calcium channel blocker amlodipine, or a combination of benazepril/amlodipine or benazepril/HCTZ on systolic blood pressure (BP) and end-organ injury (left ventricular hypertrophy, proteinuria, and endothelium-dependent relaxation to acetylcholine) in hypertensive Dahl salt-sensitive rats fed either a normal-salt (0.5% NaCl) or high-salt (4% NaCl) diet for 6 weeks. Rats fed a high-salt diet developed hypertension and significant end-organ injury. Monotherapy with HCTZ (75 mg/L in drinking water) or amlodipine (10 mg/kg/day by gavage) reduced systolic BP and proteinuria; benazepril (40 mg/kg/day by gavage) decreased proteinuria without significantly lowering systolic BP. In rats receiving a high-salt diet, only HCTZ reduced left ventricular hypertrophy, whereas endothelium-dependent relaxation was improved by amlodipine and benazepril but not by HCTZ. Combining benazepril with either amlodipine or HCTZ dramatically reduced systolic BP and end-organ injury. These data clearly support clinical studies suggesting that combination therapy is more effective than monotherapy for systolic BP control and prevention of end-organ injury. Complementary mechanisms of action of agents from different antihypertensive classes appear to facilitate the greater benefit on BP and end-organ injury.     

氯沙坦和雷米普利对压力过载引起的左心室肥厚作用的比较观察

目的：应用氯沙坦和雷米普利来探讨血管紧张肽Ⅱ对压力过载引起的左心室肥厚的相关作用。方法：采用缩窄大鼠肾动脉间腹主动脉的方法造成后负荷过载所致的左心室肥厚模型。造模后12 wk,分别给予灌服氯沙坦(1.0 mg·kg~(-1))和雷米普利(1.0 mg·kg~(-1))。给药12 wk后,应用形态测量学测定左室重量指数；Langendorff离体心脏灌流法测定离体心功能和右颈总动脉插管法测定在体心功能及血流动力学；应用酶联免疫吸附法测定大鼠血浆血管紧张肽Ⅱ(AngⅡ)、醛甾(固)酮(Ald)含量和心肌组织AngⅡ含量。结果：与模型动物比较,氯沙坦和雷米普利均能降低左室重量指数；在体大鼠血流动力学的测定中发现,压力过载造成大鼠动脉血压和左室收缩压显著升高,应用氯沙坦和雷米普利治疗后,明显改善大鼠心脏收缩功能,降低左室收缩压和外周动脉血压；离体大鼠心功能测定发现,压力过载引起离体大鼠心脏左室舒张压和左室最大上升速率下降,氯沙坦和雷米普利不能改善左室舒张压和左室最大上升速率下降。此外,氯沙坦和雷米普利能够降低心室重构过程中血浆和心肌组织中AngⅡ的含量以及血浆中Ald含量。结论：应用氯沙坦和雷米普利均能够降低缩窄大鼠腹主动脉造成的左心室肥厚,进一步提示AngⅡ在慢性压力过载导致左心室重构中起着关键性作用。     

Diminished responses to nifedipine imply severe end-organ damage in spontaneously hypertensive rats

This study was designed to investigate the effect of end-organ damage (EOD), the initial blood pressure levels, and baroreflex sensitivity (BRS) on the blood pressure-lowering effect of nifedipine in spontaneously hypertensive rats (SHRs). Nifedipine was intravenously administered at a dose of 1 mg/kg. BP was continuously recorded in the conscious state before and after nifedipine administration. BRS was determined before drug administration. Two days after the blood pressure (BP) recording, rats were killed for organ-damage evaluation. Univariate correlation analysis showed that BP changes induced by nifedipine injection were negatively correlated with EOD score and aortic weight/length but positively correlated with left kidney weight/body weight and basal BP levels. Stepwise multiple linear regression analysis demonstrated that increase in overall end-organ damage was most significantly related to the decrease in hypotensive effect of nifedipine; increase in aortic hypertrophy was also related to a decreased fall in systolic and diastolic BP induced by nifedipine, whereas increase in initial BP levels was associated with increased hypotensive effect of nifedipine. In conclusion, the severity of overall EOD contributed more than basal BP levels to the diminished responses to nifedipine, and aortic hypertrophy was also involved in diminished drug responses.     

氯沙坦对原发性高血压患者左室肥厚逆转作用

目的研究氯沙坦对原发性高血压(EH)患者的降压作用和对左室肥厚(LVH)的影响。方法选择60例EH患者,其中有LVH者22例,口服氯沙坦50 mg/d,为期6个月。观察血压,治疗前后测血脂、血糖和肝肾功能,并做二维超声心动图检测,采用自身前后对照的实验方法。结果EH患者经氯沙坦治疗前收缩压(156.9±8.9)mmHg,治疗后(138.7±1.2)mmHg。舒张压治疗前(101.3±7.5)mmHg,治疗后(85.9±6.1)mmHg,均显著下降(P<0.01)。其中LVH者左心室舒张末期内径治疗前(51.2±3.2)mm,治疗后(46.8±5.2)mm。左室重量治疗前(245.6±24.9)g,治疗后(237.1±22.4)g,均明显下降(P<0.05)。舒张末期左室后壁厚度治疗前(11.9±0.6)mm,治疗后(11.2±0.5)mm。室间隔厚度治疗前(13.4±0.8)mm,治疗后(11.7±1.5)mm。左室重量指数治疗前138.2±24.1,治疗后116.2±24.3,均明显下降(P<0.01)。结论氯沙坦治疗EH安全有效,并且可以逆转LVH。     

缬沙坦与硝苯地平控释片对高血压伴左心室肥厚逆转作用的比较

目的：评价缬沙坦与硝苯地平控释片对高血压伴左心室肥厚的逆转作用并加以比较,以便临床更好用药。方法：将60例原发性高血压伴左心室肥厚患者随机分为缬沙坦组（80mg,qd）及硝苯地平控释片组（30mg,qd）。每组30例。两组均于服药前和服药后6个月时检测血压及超声心动图。结果：两组治疗后血压较治疗前均显著降低（P〈0．01）,组间比较差异无统计学意义;治疗后超声心动图指标LVPWT、IVST、LVDd及LVMI较治疗前均明显下降（P〈0．05）,而LVMI下降尤以缬沙坦组效果更佳（P〈0．05）。结论：缬沙坦与硝苯地平控释片均具有降压和逆转左心室肥厚的作用,但缬沙坦对左心室肥厚的逆转作用相对更强,更利于临床应用。     

氯沙坦与氨氯地平的降压疗效及对左室肥厚逆转作用的比较

目的 :评价并比较氯沙坦及氨氯地平的降压疗效及对左室肥厚的逆转作用。方法 :12 0例高血压病伴左室肥厚病人随机分为 2组。氯沙坦组6 0例 ,给氯沙坦 2 5～ 50mg ,po ,qm。氨氯地平组6 0例 ,给氨氯地平 5～ 10mg ,po ,qm ;疗程均为 2 4wk。结果 :治疗 2 4wk后 ,氯沙坦组SBP和DBP下降差值分别为 (3.4± 1.7)kPa和 (2 .7± 0 .7)kPa ,氨氯地平组为 (3.2± 1.5)kPa和 (2 .2± 0 .9)kPa(均P<0 .0 1)。组间比较 ,氯沙坦组除偶测血压SBP外 ,DBP和 2 4h动态血压均较氨氯地平组下降显著 (P<0 .0 1)。2组室间隔厚度、左心室后壁厚度、左室心肌重量指数较治疗前显著改善 (P <0 .0 1)。结论 :氯沙坦与氨氯地平均能显著降压 ,并使左室肥厚逆转     

Acute inotropic effects of intravenous nifedipine and its vehicle compared with saline: a double-blind study of systolic time intervals in normal subjects.

1. The inotropic effects of intravenous nifedipine and its vehicle were studied noninvasively in a double-blind placebo controlled crossover fashion using systolic time intervals in 12 normal subjects. 2. Nifedipine caused vasodilation, a fall in systolic and diastolic blood pressure, and increased heart rate. The vehicle alone caused vasodilation and decreased systolic blood pressure, without a change in heart rate. 3. Nifedipine increased left ventricular ejection time (LVET) and decreased pre-ejection period (PEP) and the ratio PEP/LVET, whereas the vehicle alone had the opposite effect. Neither treatment affected the total duration of electromechanical systole. 4. These results suggest that the vehicle has a negative inotropic effect, which is overcome by the indirect positive inotropic effect of nifedipine when they are administered together systemically.     

Changes in left ventricular mass during a double-blind study with chlorthalidone and slow-release nifedipine

Summary The presence of a possible correlation between changes in left ventricular mass of hypertensive patients and the degree of blood pressure reduction with different antihypertensive drugs has been investigated in 40 outpatients by M-mode echocardiography. Ten of these, with blood pressure in normal limits with different antihypertensive treatment had their therapy changed in chlorthalidone 25 mg/day without any run-in (Group A); other 30 patients, with a previously uncontrolled blood pressure, after a 14 day run-in, were randomly allocated to chlorthalidone 25 mg/day (Group B), slow release nifedipine 20 mg/day (Group C) or placebo (Group D). At the end of the eight week treatment period a further decrease in systolic blood pressure was observed in Group A without changes in ventricular mass; an highly significant decrease in both systolic and diastolic blood pressure was observed in B and C but only patients on chlorthalidone changed their ventricular mass; no change in both blood pressure and ventricular mass was observed on placebo. As changes in ventricular mass are not correlated with blood pressure reduction, we conclude that other, not well defined factors, apart from the decrease in duration and degree of left ventricular systolic wall tension, may be responsable for reversal of left ventricular hypertrophy.     

洛沙坦抗高血压及左室肥厚的疗效观察

目的 :观察血管紧张素 受体拮抗剂—洛沙坦的降压效果及对高血压病合并左室肥厚的影响。方法 :4 6例合并左室肥厚的 期高血压病患者服用洛沙坦 5 0 mg/ d,观察其血压的变化及治疗前和 6个月后左室质量 (L VM)。结果 :用洛沙坦后 4 d～ 6d血压开始下降 ,2周血压趋向正常 ,4周血压继续缓慢下降 ,6周时达到最大降压效果。 L VM在 12周时无明显变化。 2 4周表现轻度 L VM减少。结论 :洛沙坦是抗高血压的一个有效治疗药物 ,对左心室肥厚有轻度逆转作用     

阿托伐他汀联合氯沙坦钾治疗高血压伴左心室肥厚疗效分析

目的研究阿托伐他汀联合氯沙坦钾治疗高血压伴左心室肥厚的疗效。方法将130例血脂正常的高血压伴左心室肥厚患者按随机数字表法分为2组,每组65例。对照组患者给予氯沙坦钾治疗,治疗组给予阿托伐他汀联合氯沙坦钾治疗。两组均治疗随访1年,检测治疗前、后血压变化、左心室舒张末期内径、室间隔厚度、左心室舒张末期后壁厚度、左心室重量指数变化。结果治疗后,治疗组的收缩压、舒张压分别为(124.1±16.3)、(78.1±13.5)mmHg,对照组分别为(126.4±18.5)、(79.1±13.6)mmHg,两组比较差异无统计学意义(P>0.05);治疗组左心室舒张末期内径、室间隔厚度、左心室舒张末期后壁厚度、左心室重量指数分别为(43.2±5.5)mm、(11.3±1.5)mm、(11.0±1.6)mm、(102.1±14.7)g/m2,对照组分别为(48.5±5.4)mm、(13.9±1.7)mm、(12.0±1.7)mm、(112.6±18.7)g/m2,两组比较差异有统计学意义(P<0.05或P<0.01)。结论阿托伐他汀联合氯沙坦钾降压疗效显著,能逆转高血压所致的左心室肥厚,长期服用可以减少心血管事件的发生。     

氯沙坦治疗高血压病伴左室肥厚患者的疗效观察

目的观察氯沙坦对高血压病伴左室肥厚患者降压及左室肥厚的治疗效果。方法高血压病伴左室肥厚患者60例,随机分为氯沙坦组（30例）和卡托普利组（30例）,用药前及用药后3个月测量血压和计算患者左室质量指数。结果2组用药后血压和左室质量指数均比用药前有显著的下降（P〈0.01）,但组间差异无统计学意义（P〉0.05）。结论氯沙坦可有效降低高血压病伴左室肥厚患者的血压,逆转左心室肥厚。     

硝苯地平对肾性高血压儿童左室肥厚的影响

目的:了解硝苯地平对肾性高血压患儿左室肥厚的影响。方法:超声观察18例患儿药物治疗8w前后左室重量指数(LVMI),并与15例正常儿童作比较。结果:与正常对照组(32.24±11.22g/m2)相比,治疗前患儿的LVMI增大(52.32±13.32g/m2)(P<0.05),血压增高,但年龄、血脂、血糖无显著性差异(P>0.05)。治疗后患者血压下降,LVMI显著减小(33.43±12.01g/m2)(P<0.01)。结论:硝苯地平可以在有效降低血压的同时抑制患儿左室肥厚,这一作用并不与血脂、血糖水平有关。     

Beneficial effects of the combination of amlodipine and losartan for lowering blood pressure in spontaneously hypertensive rats

A combination of antihypertensive agents can better control blood pressure and reduce the number and severity of side effects than a monotherapy. Since both CCBs (calcium channel blockers) and ARBs (angiotensin II receptor type-1 blockers) are current and effective antihypertensive drugs, this study assessed the synergistic antihypertensive effects as well as the optimal combination ratio of these two drugs. Amlodipine (3 mg/kg) or losartan (30 mg/kg) alone or a combination of each drug at a ratio 1:10 and 1:20 was administered orally to spontaneously hypertensive rats (SHR). A four-week treatment of either 3 mg/kg amlodipine or 30 mg/kg losartan alone decreased the systolic blood pressure (SBP). However, their combination significantly lowered the SBP from the 3^rd week, and there was a positive correlation between this reduction in blood pressure and the improvement in arterial endothelium-dependent relaxation. In addition, the combination therapy (1:20) decreased both the cardiac mass and left ventricular weight to a greater extent than with either amlodipine or losartan alone. The collagen content in the cardiac tissue was also significantly lower after the 4-week combination therapy (1:10). These results suggest that the combined use of amlodipine and losartan might be more effective in treating hypertension than a monotherapy.     

氯沙坦对老年高血压者左室肥厚逆转及血浆内皮素水平的影响

目的 :了解氯沙坦对老年高血压性左室肥厚的逆转作用及对血浆内皮素 (ET)水平的影响。方法 :以 2 0例健康老年人为对照组 ,观察单纯高血压 32例 (EH组 )、高血压伴左室肥厚 2 6例 (LVH组 )在每日服氯沙坦 50mg前及 16wk后血压、ET的变化。用超声心动图观察LVH组在用药前后的左室舒张末期内径 (LVDd)、室间隔厚度 (IVST)、左室后壁厚度 (LVPWT)、左室重量 (LVM )、左室重量指数 (LVMI)的变化。结果 :经氯沙坦治疗后 ,EH组、LVH组的平均动脉压 (MAP)及ET水平有显著性下降 ;LVH组的ET水平与LVM ,LVMI呈正相关 ,LVH组在治疗后IVST ,LVPWT ,LVDd ,LVM ,LVMI亦有显著性下降。结论 :氯沙坦对老年高血压病人不仅有良好的降压效果 ,同时具有逆转LVH及降ET的作用     

Comparison of haemodynamic effects of nifedipine and molsidomine in patients with coronary artery disease

Summary The haemodynamic effects of oral nifedipine 20 mg and molsidomine 4 mg were compared in 24 patients with coronary artery disease.Molsidomine unlike nifedipine caused a significant fall in mean pulmonary artery pressure and left ventricular end-diastolic pressure. Both drugs caused a significant and comparable reduction in systolic and diastolic blood pressure. Although only nifedipine significantly reduced systemic vascular resistance the difference between the drugs was not significant. The heart rate was significantly increased by nifedipine but not by molsidomine. The ejection phase indices were all increased by molsidomine and the increment in the mean normalized systolic ejection rate was significantly greater than that due to nifedipine. The left ventricular end-systolic volume index decreased significantly after molsidomine but not nifedipine.Neither drug significantly affected left ventricular end diastolic volume index, stroke volume index, maximal rate of rise of left ventricular pressure or left ventricular stroke work index.     

Influence of nifedipine on ventricular function and myocardial hypertrophy in spontaneously hypertensive rats

We compared left ventricular (LV) hemodynamics, LV muscle mass (LVMM), and LV geometry of 13 spontaneously hypertensive rats (SHRs) treated for 20 weeks with nifedipine (30 mg/kg/day) with those of 11 age-matched untreated SHRs. LVMM, LVMM related to end-diastolic volume (LVMM/EDV), LV pressure (PLV), systolic wall stress (Tsyst), ejection fraction (EF), cardiac index (CI), and isovolumetric contractility indices (dP/dtmax, IP, t-dP/dtmax, and VCE) were determined. Nifedipine treatment lowered PLV from 170 to 136 mm Hg and Tsyst from 222 to 194 10(3) dyn/cm2. LVMM and LVMM/EDV decreased moderately from 800 to 744 mg and from 2.56 to 2.29 mg/microliter, respectively. Left ventricular ejection was markedly increased (EF from 52 to 64%; CI from 154 to 178 ml/min X kg), whereas isovolumic contractility indices remained unchanged. Thus, nifedipine reduced but did not totally prevent myocardial hypertrophy and enhanced LV function. These effects seem to result from reduction in LV afterload and not from altered myocardial contractility.     

依那普利和氯沙坦治疗中重度高血压的疗效观察

目的：评价依那普利和氯沙坦联用对中度重度高血压患者的降压效果和左心室肥厚的逆转作用。方法：对36例中重度高血压患者给予口服依那普利5－10mg/日和氯沙坦25－50mg/日,监测血压、心率及行超声心动图检查。结果：经治疗患者血压、心率明显下降,IVST、LVPWT和LVMI明显减少（P＜0．01）。结论：依那普利和氯沙坦联用能有效降低血压及逆转心室肥厚,且两药单独用量少,副作用少。