Fosinopril improves left ventricular diastolic function in young mildly hypertensive patients without hypertrophy

To clarify whether fosinopril monotherapy can improve left ventricular diastolic function (LVDF) in young mildly hypertensives without hypertrophy, we studied 66 patients (pts) with diastolic blood pressure 90–100 mmHg, aged <45 years, with normal 2-dimensional echocardiography (2-D echo), and impaired DF. Impaired DF was defined as a Doppler transmitral early (E) to atrial (A) filling velocity ratio (E/A ratio) <1. Thirty-eight pts were selected for fosinopril monotherapy. Mean age was 36 years. Duration of documented hypertension was 5.4 years. Mean daily dose of fosinopril was 20 mg. Twenty-eight controls were treated with hydrochlorothiazide and hydralazine combination. Sixty-six age- and sex-matched healthy subjects served to establish normal reference values of 2-D and Doppler echo measurements. All hypertensives were treated for 30 months and re-examined 4 weeks after cessation of treatment. The fosinopril-treated group showed improvements in transmitral E (52 ± 8 cm/s, vs. 61 ± 9 cm/s, p < 0.01), A (56 ± 9 cm/s, vs. 47 ± 6 cm/s, p < 0.05), and E/A ratio (0.93 ± 0.16, vs. 1.29 ± 0.18, p < 0.01). Moreover, the early to atrial velocity-time integral ratio (1.31 ± 0.10, vs. 2.24 ± 0.10, p < 0.001) improved. The pulmonary venous flow pattern normalized after fosinopril therapy. LV mass index, relative wall thickness, LV dimension, left atrial dimension, fractional shortening, heart rate, and body mass index did not change. The hydrochlorothiazide-hydralazine combination-treated group did not show an improved diastolic function. It is concluded that long-term fosinopril monotherapy leads to an improvement of impaired LVDF in young mildly hypertensives without hypertrophy.     

Influence of tissue affinity of angiotensin-converting enzyme inhibitors on left ventricular remodeling after myocardial infarction

Background: The demonstration of local renin-angiotension systems has raised the question of whether angiotensinconverting enzyme (ACE) inhibitors with different tissue affinities differ with regard to their effects on postinfarction remodeling. Hypothesis: The study was undertaken to investigate the influence of ACE inhibitors with different tissue affinity on morphology and function of the infarcted left ventricle. Methods: In all, 52 patients (17 women, 35 men, 38-73 years) with large acute myocardial infarction were randomized to receive either 25-75 mg/day captopril or 10-20 mg/day fosinopril beginning on the Day 7 after infarction. Of these, 28 had anterior and 24 had posterior wall infarctions. Infarct size was determined by the creatine kinase integral method. Fifty patients were examined by cinemagnetic resonance imaging (CMRI) 1 and 26 weeks after infarction. The following parameters were determined: left ventricular enddiastolic and end-systolic volume index (LVEDVI, LVESVI), ejection fraction (LVEF), infarct weight, and muscle mass (LVMM). The volume-to-mass ratio (VMR) was calculated and the clinical status according to the guidelines of the New York Heart Association (NYHA) was documented at each examination time. The results were compared with those of a historical sample without ACE-inhibitor therapy examined in an identical manner (n = 31, 10 women, 21 men, 36-75 years). Results: LVEDVI and LVESVI increased in the first 6 months after infarction by 24.9 and 36.6%, respectively, in the historical sample; by 11.0 and 7.8%, respectively, under captopril; and by 13.1 and 10.7%, respectively, under fosinopril. LVEF decreased by 14.9% in the untreated sample, by 3.7% under captopril and by 5.0% under fosinopril. Infarct weight and LVMM increased by 12.7 and 15.3%, respectively, without ACE inhibition, by 5.7 and 10.1%, respectively, in patients treated with captopril, and by 6.1 and 9.3%, respectively, in patients treated with fosinopril. The VMR increased by 7.4% in the historical sample, by 3.5% in the captopril group, and by 1.8% in the fosinopril group. The NYHA clinical status improved by 18.2% without ACE inhibition, by 42.9% in the captopril group, and by 26.3% in the fosinopril group. The differences between the two ACE-inhibitor groups and the reference group were all significant, while the differences between the captopril group and the fosinopril group were significant only for VMR (p<0.01) and NYHA class (p < 0.05). Conclusions: Both captopril and fosinopril have a comparable positive influence on postinfarction remodeling and on clinical status. Lipophilicity and tissue affinity do not seem to play a clinically important role in ACE-inhibitor therapy after infarction.     

福辛普利防治心肌肥厚和钙超载的实验研究

目的　研究福辛普利对鼠实验性高血压心肌肥厚及钙超载的影响。方法　以腹主动脉部分狭窄大鼠为模型 ,观察福辛普利对血压、心肌重量及超微结构、钙含量、肌浆网钙泵功能的影响。结果　福辛普利组大鼠心肌超微结构和钙泵功能保持稳定 ,心肌重量和钙含量明显低于安慰剂组 (P<0 .0 5 )。结论　福辛普利不仅能防治心肌肥厚 ,而且能保护肌浆网钙泵功能 ,防止心肌钙超载损伤     

福辛普利联合氨氯地平对糖尿病合并高血压患者血清转化生长因子-β1、醛固酮和C反应蛋白的影响

目的 探究福辛普利联合氨氯地平对糖尿病并发原发性高血压(高血压)患者血清转化生长因子-β1(transforming growth factor-β1,TGF-β1)、醛固酮和C反应蛋白(C-reactive protein,CRP)的影响.方法 选取青岛思达心脏医院2018年1月～2019年1月收治的136例糖尿病并...     

用两种剂量福辛普利治疗重症心力衰竭患者的临床研究

目的：比较两种剂量福辛普利治疗重症心力衰竭(HF)的临床疗效、安全性和防治心血管事件的作用。方法：将85例NYH心功能Ⅲ，Ⅳ级重症HF患随机单盲分为2组：福辛普利20mg／d组43例；福辛普利10mg/d组42例，治疗1年，观察患心功能、不良反应和心脏性事件发生情况。结果：福辛普利治疗重症HF3、12个月，2组均能明显改善心功能。包括临床症状改善总有效率，超声心动图左心室射血分数(LVEP)、左心室短轴缩短率(FS)、二尖瓣快速充盈期和心房收缩期二尖瓣血流速度(E／A)，也能降低纤溶系统的纤溶酶原激活物抑制剂—1(PAI—1)、纤维蛋白原(FG)、C—反应蛋白(CRP)、且20mg／d组对上述指标改善均优于10mg／d组，(P＜0．05)，同时20mg／d组治疗3，12个月发生不稳定型心绞痛(UP)，心律失常事件比10mg／d组明显减少(P＜0．05)，而2组治疗后3，12个月血压及心率均较治疗前明显下降(P＜0．05)，但无组间差异(P＜0．05)，2组不良反应轻微。结论：用福辛普利20mg／d治疗重症HF，预防心脏性事件较合适，需否用40mg 1次／d，仍需临床探讨。     

Effects of fosinopril and valsartan on expressions of ICAM-1 and NO in human umbilical vein endothelial cells

Objective To investigate the effects of fosinopril and valsartan on the expression of intercellular adhesion molecule-1 ( ICAM-1 ) and nitric oxide ( NO ) induced by oxidized low-density lipoprotein(ox-LDL) in human umbilical vein endothelial cells.Methods The levels of NO, ICAM-1, and nitric oxide synthase (NOS) were determined using the nitrate reductase method, ELISA, immunohistochemical and image analyses.Results The ox-LDL can significantly increase the expression of ICAM-1 and inhibit the expression of NO and NOS in a dose-dependent manner. Fosinopril and valsartan can significantly inhibit these roles of ox-LDL. The roles of fosinopril and valsartan were not significantly different.Conclusion Fosinopril and valsartan inhibit oxidized LDL-induced expression of ICAM-1 and increase the expression of NO in human umbilical vein endothelial cells, which is one of the mechanisms of antiatherosclerosis.     

坎地沙坦和福辛普利联合治疗高血压伴早期糖尿病肾病

目的研究坎地沙坦和福辛普利联合治疗高血压伴早期糖尿病肾病(DN)及糖尿病高血压的疗效。方法随机选择门诊长期随访的2型糖尿病并早期DN及糖尿病高血压患者60例,随机分为福辛普利组、坎地沙坦组与联合治疗组(福辛普利+坎地沙坦),观察16周。检测各组治疗前后尿素氮(BUN)、血清肌酐(SCr)及尿清蛋白排泄率(UAER)水平;并监测其治疗前后平均动脉压(MAP)水平。结果3组治疗前后MAP水平差异无统计学意义,但治疗后尿清蛋白排泄率均较治疗前明显下降(P<0.05);联合治疗组尿清蛋白排泄率下降最明显(P<0.05)。结论福辛普利和坎地沙坦联合治疗早期糖尿病肾病疗效显著。     

Passive and Carrier-Mediated Intestinal Absorption Components of Two Angiotensin Converting Enzyme (ACE) Inhibitor Prodrugs in Rats: Enalapril and Fosinopril

The intestinal absorption mechanism of two ACE inhibitor prodrugs, enalapril and fosinopril, was investigated in rats using a single-pass perfusion method. A modified boundary layer solution was applied to determine the apparent intestinal wall permeability. The prodrug enalapril is well absorbed from rat jejunum, whereas the parent drug, enalaprilat, is poorly absorbed. The permeability of enalapril is concentration dependent and is decreased by the dipeptide Tyr-Gly and by cephradine but not by the amino acids L-leucine or L-phenylalanine, indicating a nonpassive absorption mechanism via the small peptide carrier-mediated transport system. In contrast, fosinopril is readily absorbed by a concentration-independent mechanism without the involvement of the peptide carrier.     

3种转换酶抑制剂治疗原发性高血压的成本-效果分析

目的 :探讨3种转换酶抑制剂治疗原发性高血压所产生的经济效果。方法 :选择186例原发性高血压患者 ,随机分为3组 ,分别给予依那普利、福辛普利、培哚普利 ,运用药物经济学方法进行分析。结果 :依那普利为治疗原发性高血压成本最小的药物。结论 :运用药物经济学的分析方法可使有限资源得到合理配置     

福辛普利对大鼠血管球囊损伤后血管紧张肽Ⅱ1型受体表达的影响

目的 :研究血管紧张肽转换酶 (ACE)抑制剂福辛普利 (fosinopril)对血管球囊损伤后血管紧张肽Ⅱ 1型受体 (AT1R)表达的影响。方法 :采用免疫组织化学技术SP法检测在大鼠髂动脉球囊损伤模型 (Clowes法[1] )中福辛普利干预后局部AT1R表达的变化。结果 :球囊损伤后d 1 4,血管中层AT1R表达 (0 .1 2 0±0 .0 1 0 )比假手术组 (0 .1 0 2± 0 .0 2 1 )显著增多 (P <0 .0 5 ) ,而此时内膜层AT1R(0 .2 82±0 .0 1 6)为中层的 2倍以上 ,福辛普利使球囊损伤后d 1 4血管AT1R(中层 0 .0 86± 0 .0 2 2 ,内膜层 0 .1 74±0 .0 1 8)表达显著减少 (P <0 .0 1 )。结论 :福辛普利能降低血管球囊损伤后AT1R表达