坎地沙坦酯治疗老年患者原发性高血压的疗效及安全性分析

目的:探讨坎地沙坦酯治疗老年高血压患者的疗效和安全性。方法:选取我院110例老年原发性高血压患者,随机分为观察组(坎地沙坦酯治疗)和对照组(依那普利治疗),对比分析两组患者药物治疗前、后的动态血压监测及相关指标。结果:经两个月治疗后,两组患者坐位收缩压(SBP)及舒张压(DBP)谷值均较基线明显降低,观察组下降幅度明显大于对照组,差异有统计学意义(P0.05);观察组的总有效率为90.91%,明显高于对照组的76.36%,差异有统计学意义(P0.05)。结论:坎地沙坦酯治疗老年患者原发性高血压疗效显著,可明显降低收缩压和舒张压,是治疗老年性高血压理想的制剂。     

依那普利叶酸片对高血压伴高同型半胱氨酸血症大鼠左室肥厚干预的研究

目的:观察高同型半胱氨酸对高血压大鼠心肌内质网应激相关因子GRP94、caspase12表达的影响,及依那普利叶酸片(简称依叶片)对其表达的干预作用。方法:30只雄性成年自发性高血压大鼠(SHR),随机分为对照组、模型组和依叶片组,每组10只。对照组给予普通颗粒饲料喂养同时给予双蒸水灌胃,模型组给予含3%蛋氨酸的颗粒饲料喂养同时给予双蒸水灌胃,依叶片组给予含3%蛋氨酸的颗粒饲料喂养同时给予依叶片粉剂20 mg/kg/d灌胃。实验第8周末,用颈动脉插管法测各组大鼠平均动脉压(MAP),同型半胱氨酸检测仪检测血清同型半胱氨酸(homocystein,Hcy)浓度,称取体质量、全心质量及左心室质量计算大鼠心肌肥厚指数HWI及LVEI,通过HE染色观察心肌细胞形态学改变,免疫组化检测大鼠心肌组织中GRP94及caspase12表达水平。结果:①大鼠血清Hcy水平的变化。对照组大鼠血清Hcy值在正常值范围。与对照组相比,模型组大鼠血清Hcy值显著增高(P0.01);与模型组相比,依叶片组大鼠血清Hcy值明显降低(P0.01)。②大鼠HWI、LVEI及MAP的变化。模型组大鼠的HWI及LVEI均明显高于对照组(P0.05);依叶片干预后大鼠的HWI及LVEI均明显降低(P0.05)。对照组与模型组大鼠的MAP均明显增高,但两组大鼠的MAP差异无统计学意义(P0.05);与模型组相比,依叶片干预后大鼠的MAP明显降低(P0.01)。③大鼠心肌细胞内质网应激(endoplasmic reticulum stress,ERS)相关因子GRP94及caspase12表达。对照组及模型组大鼠心肌细胞GRP94及caspase12表达均增高。与对照组相比,模型组大鼠心肌细胞GRP94、caspase12表达增高更为明显(P0.05)。依叶片干预后大鼠心肌细胞GRP94、caspase12表达明显降低(P0.05)。结论:高Hcy通过ERS途径使高血压大鼠左室肥厚程度加重;依叶片可有效降低血清Hcy及血压水平,抑制心肌细胞ERS,从而有效逆转左室肥厚,其对左室肥厚干预的分子机制为"H型"高血压的预防及治疗提供了新的理论依据。     

International Society of Chronobiology: Membership Information

The International Society for Chronobiology has as its aims, furthering the study of temporal changes in living matter, including biological rhythms in development and ageing in individuals and populations; studying and defining the mechanisms of temporal changes; fostering practical applications for chronobiological findings to mankind in basic and applied biology, physiology, work hygiene and the medical sciences; promoting education in and wide understanding of chronobiology; and furthering contact between scientists in the field and providing a forum for practitioners of chronobiology.     

依那普利在大鼠单侧输尿管梗阻再通模型中的抗纤维化作用

目的:探讨依那普利对大鼠单侧输尿管梗阻再通模型肾脏纤维化的影响.方法:18只SD大鼠随机分为两组:假手术组(6只)以及单侧输尿管梗阻模型组(12只).输尿管梗阻3天后,实施梗阻再通手术,再将大鼠随机分为模型组(6只)以及依那普利组(6只),术后,依那普利组给予依那普利灌胃10mg/kg/d,假手术组以及模型组给予等量0.5%CM-CNa溶液灌胃.用药2周后,取术侧肾组织做HE染色,并采用Raford评分系统对肾间质损伤程度进行评分;用Real-timePCR方法检测Ⅰ、Ⅲ型胶原以及CT-GFmRNA的表达;用Westemblot方法检测CTGF蛋白水平的表达.结果:模型组大鼠肾脏损伤程度,Ⅰ、Ⅲ型胶原mRNA表达水平,以及CTGFmRNA和蛋白表达水平均比假手术组明显上升(P<0.01).经依那普利治疗后,与模型组相比,以上指标均显著下降(P<0.01).结论:依那普利能有效阻止大鼠单侧输尿管梗阻再通后肾脏纤维化的进展.依那普利抗纤维化的作用机制可能与抑制CTGF的表达有关.     

氨氯地平联合依那普利治疗原发性高血压的临床疗效及对患者左心室肥厚的影响

摘要目的：探讨氨氯地平联合依那普利治疗原发性高血压的临床效果,观察联合用药对左心室肥厚的影响。方法：选择本院收治的原发性高血压患者92例,随机分为观察组和对照组,各46例,对照组给予苯磺酸左旋氨氯地平5mg,1次／d,口服;观察组在对照组基础上加用马来酸依那普利10mg,2次／d,口服,疗程均为24周。观察两组治疗前后血压变化,应用超声心动图测量两组左心室厚度变化。结果：治疗后,观察组总有效率为91_3％;对照组总有效率为73．9％,观察组总有效率高于对照组（P〈0．05）。治疗前两组心率、血压比较无统计学差异（P〉0．05）,治疗后两组血压均明显降低,观察组收缩压、舒张压明显低于对照组（P〈O．05）;观察组心率明显低于对照组（P〈0．01）。治疗前两组左心室舒张末期室间隔厚度（Leaventricularend—diastolicventricularseptalthickness,IVST）、左心室后壁厚度（1eftventricularposteriorwallthickness,U,PwT）和左室射血分数（Leftventricularejectionfxaction,LVEF）比较无统计学差异（P〉0．05）;治疗后观察组IVST、L、,PwT明显低于对照组,LVEF明显高于对照组（P〈0．05）。结论：氨氯地平联合依那普利治疗原发性高血压能有效扭转左心室肥厚,降压效果较单独应用氨氯地平更佳。     

依那普利与二甲双胍联合治疗肥胖性高血压的临床观察

目的:肥胖与高血压的发生、发展密切相关,肥胖人群更容易发生高血压,而目前我国肥胖和高血压的发生率大幅上升,至今仍无针对肥胖性高血压的指南。研究表明,二甲双胍有改善代谢以外的降压作用,ACEI有降压以外的改善代谢作用。本研究的目的为观察二甲双胍联合依那普利对肥胖性高血压患者血压、体重指数(BMI)、腰围及血脂的影响效果。方法:76例诊断为肥胖性高血压的患者随机分成观察组和对照组,观察组38例患者给予二甲双胍+依那普利治疗;对照组38例患者给予依那普利治疗,观察期为24周,并于治疗前及治疗24周后测定血脂(TG、TC、HDL-C、LDL-C)、BMI、腰围(WC)变化。每2周门诊随访并记录血压。结果:①经24周治疗后,两组患者血压(MDBP、MSBP)均明显降低,P<0.05,且二甲双胍+依那普利观察组的降压作用明显优于依那普利对照组(P<0.05);②观察组的体重指数(BMI)、腰围(WC)、血脂水平(TC、TG、HDL-C、LDL-C)较治疗前显著下降(P<0.05),而对照组较治疗前无明显变化(P>0.05)。结论:二甲双胍+依那普利对肥胖性高血压患者不仅具有良好的降压效果作用而且能降低BMI,WC及血脂水平。是肥胖性高血压较理想的治疗方案。     

Circadian Rhythm of Blood Pressure in Congestive Heart Failure and Effects of ACE Inhibitors

In 33 patients with heart failure (NYHA 11-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:OO to 22:OO h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 ± 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 ± 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p < 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 ± 0.1 mmol/L) reached statistical significance (p < 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 ± 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.     

Effect of paricalcitol and enalapril on renal inflammation/oxidative stress in atherosclerosis

AIM: To investigate the protective effect of paricalcitol and enalapril on renal inflammation and oxidative stress in Apo E-knock out mice. METHODS: Animals treated for 4 mo as group(1) Apo E-knock out plus vehicle, group(2) Apo E-knock out plus paricalcitol(200 ng thrice a week),(3) Apo Eknock out plus enalapril(30 mg/L),(4) Apo E-knock out plus paricalcitol plus enalapril and(5) normal. Blood pressure(BP) was recorded using tail cuff method. The kidneys were isolated for biochemical assays using spectrophotometer and Western blot analyses. RESULTS: Apo E-deficient mice developed high BP(127 ± 3 mm Hg) and it was ameliorated by enalapril and enalapril plus paricalcitol treatments but not with paricalcitol alone. Renal malondialdehyde concentrations, p22 phox, manganese-superoxide dismutase, inducible nitric oxide synthase(NOS), monocyte chemoattractant protein-1, tumor necrosis factor-alpha and transforming growth factor-β1 levels significantly elevated but reduced glutathione, Cu Zn-SOD and e NOS levels significantly depleted in Apo E-knock out animals compared to normal. Administration of paricalcitol, enalapril and combined together ameliorated the renal inflammation and oxidative stress in Apo E-knock out animals. CONCLUSION: Paricalcitol and enalapril combo treatment ameliorates renal inflammation as well as oxidative stress in atherosclerotic animals.     

Enalapril inhibits nuclear factor-κB signaling in intestinal epithelial cells and peritoneal macrophages and attenuates experimental colitis in mice

Aims

Enalapril, an angiotensin-converting enzyme (ACE) inhibitor, has pleiotropic effects such as anti-inflammatory effects. This study investigated the effect of enalapril on the nuclear factor-kappa B (NF-κB) pathway and on experimental colitis.

Main methods

The human intestinal epithelial cell (IEC) line COLO 205 and peritoneal macrophages from C57BL/6 wild-type mice and IL-10-deficient (IL-10^−/−) mice were prepared and subsequently stimulated with lipopolysaccharide (LPS) alone or LPS plus enalapril. The effect of enalapril on NF-κB signaling was examined by western blotting to detect IκBα phosphorylation/degradation; an electrophoretic mobility shift assay (EMSA) to assess the DNA binding activity of NF-κB; and ELISAs to qualify IL-8, TNF-α, IL-6, and IL-12 production. In in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis in wild-type mice and chronic colitis in IL-10^−/− mice were treated with or without enalapril. Colitis was quantified by histologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry.

Key findings

Enalapril significantly inhibited LPS-induced IκBα phosphorylation/degradation, NF-κB binding activity, and pro-inflammatory cytokine production in both IEC and peritoneal macrophages. The administration of enalapril significantly reduced the severity of colitis, as assessed based on histology in both murine colitis models. Furthermore, in colon tissue, the up-regulation of IκBα phosphorylation with colitis induction was attenuated in enalapril-treated mice.

Significance

Enalapril may block the NF-κB signaling pathway, inhibit the activation of IECs and macrophages, and attenuate experimental murine colitis by down-regulating IκBα phosphorylation. These findings suggest that enalapril is a potential therapeutic agent for inflammatory bowel disease.     

Mixed-Type Inhibition of Pulmonary Angiotensin I-Converting Enzyme by Captopril,Enalaprilat and Ramiprilat

Abstract

We have compared at the enzymological level pulmonary angiotensin I-converting enzymes (ACE) purified to electrophoretic homogeneity from four mammalians species: pig, rat, monkey and human. Using both substrates hippuryl-histidyl-Ieucine and furylacryloyi-phenylal-anyl-glycyi-glycine in steady-state conditions, all the ACES exhibited Michaelis kinetics with identical Michaelis constants, maximal velocities, optimal pH and optimal activating chloride-concentrations. The apparent inhibitory constant was higher for Captopril than for Enalaprilat and even more so for Ramiprilat irrespective of the origin of ACE and the substrate used. Although these inhibitors have been described as competitive inhibitors, Lineweaver-Burk plots were not in accordance with a simple competitive model; moreover, Dixon plots were rather characteristic of non-competitive inhibition. These data emphasize the hypothesis that ACE inhibitors act with mixed-type inhibition, which is consistent with their slow-tight binding to the ACE active center, also with binding of chloride on a critical lysine residue leading to a potential conformational change, and finally with the fact that ACE has two domains, each bearing one catalytic site. On the other hand, as identical kinetic parameters were obtained on the different ACE preparations, results from animal models should allow the extrapolation to humans, in particular for investigations on both renin-angiotensin and kallikrein-kinin systems, and on their inhibition.