赖诺普利对高血压患者胰岛素样生长因子-1水平和左室重构的干预

目的:观察用赖诺普利治疗轻中度原发性高血压患者6个月前后血清胰岛素样生长因子-1的水平及左室质量指数的变化。方法:用放射免疫法检测原发性高血压患者60例(EH组)和健康者60例(NC组)血清胰岛素样生长因子-1水平,以超声测定两组的左室质量指数,并观察EH组用赖诺普利治疗6个月前后二者的改变。结果:EH组血清胰岛素样生长因子-1水平为(207.70±79.21)μg/L,明显高于NC组(132.53±35.62)μg/L(P<0.01);左室质量指数分别为150.67±25.48、101.32±13.56(P<0.05)。赖诺普利治疗6个月后,血清胰岛素样生长因子-1水平降至(156.82±36.40)μg/L(P<0.01),左室质量指数下降至112.01±22.34(P<0.05)。结论:EH组患者血清胰岛素样生长因子-1及左室质量指数水平升高,赖诺普利治疗可使胰岛素样生长因子-1水平降低,并逆转左室肥厚。     

赖诺普利治疗系统性红斑狼疮患者尿蛋白的临床研究

目的探讨赖诺普利对系统性红斑狼疮(SLE)患者尿蛋白的作用。方法将72例SLE患者随机分为两组,赖诺普利治疗组(治疗组)39例及非赖诺普利治疗组(对照组)33例。治疗组给予赖诺普利10 mg/d,总疗程为8周。治疗8周后,与治疗前及对照组比较,观察24 h尿蛋白定量等指标的变化。结果在降尿蛋白的疗效比较中,治疗组显著优于对照组(P<0.01)。治疗组在治疗后24 h尿蛋白明显下降(P<0.01)。对照组下降不明显(P>0.05)。两组血压均有下降,但差异无统计学意义(P>0.05)。主要不良反应是咳嗽、血钾轻度升高,但不影响治疗。结论赖诺普利可有效地降低SLE患者的尿蛋白,对SLE患者的肾脏有较好的保护作用。     

加校正因子的主成分自身对照法测定赖诺普利氢氯噻嗪片中有关物质的含量

目的:建立加校正因子的主成分自身对照法测定赖诺普利氢氯噻嗪片中有关物质的含量。方法:Ultimate XBC18色谱柱(4.6 mm×250 mm,5μm),流动相0.05 mol·L-1磷酸盐缓冲溶液(pH7.3±0.1)-乙腈(85∶15),流速1.0 mL·min-1,检测波长210 nm,柱温30℃,进样量10μL。测定赖诺普利及其杂质赖诺普利相关物质A,氢氯噻嗪及其杂质苯并噻二嗪相关物质A的线性方程,以斜率计算杂质相对于主成分的校正因子,用相对保留时间确定各杂质位置。其他有关物质的含量采用自身对照法计算。结果:赖诺普利相关物质A和苯并噻二嗪相关物质A的相对保留时间分别为1.88,0.69,校正因子分别为1.16,0.87。3批样品中苯并噻二嗪相关物质A的质量分数分别为0.671%,0.673%,0.660%,其他杂质均低于检测限。结论:该方法简便快速,可准确测定赖诺普利氢氯噻嗪片中有关物质的含量。     

Efficacy and Tolerability of Delapril Plus Indapamide Versus Lisinopril Plus Hydrochlorothiazide Combination Treatments in Mild to Moderate Hypertension: A Multicenter, Randomized Clinical Study

Background: Several studies have shown that antihypertensive monotherapy is commonly insufficient to control blood pressure (BP) in hypertensive patients and that concomitant use of ≥2 drugs is necessary in ∼50% of these patients. The combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic, delapril plus indapamide (D + I), has been shown to be effective and tolerable, with no interaction between the 2 components. Another widely used combination of ACE inhibitor and diuretic is lisinopril plus hydrochlorothiazide (L + H).Objectives: The aims of this study were to confirm the antihypertensive efficacy and tolerability of the fixed combination of D + I in mild to moderate hypertension, and to compare its therapeutic efficacy and tolerability with that of L + H.Methods: The antihypertensive efficacy and tolerability of a fixed combination of D + I (30-mg + 2.5-mg tablets once daily) or L + H (20-mg + 12.5-mg tablets once daily) in patients with mild to moderate hypertension were compared in a multinational, multicenter, randomized, 2-armed, parallel-group study. Eligible patients were aged 18 to 75 years and had a diastolic blood pressure (DBP) 95 to 115 mm Hg and a systolic blood pressure (SBP) ≤180 mm Hg, both measured in the sitting position. After a single-blind, placebo run-in period of 2 weeks, patients were randomized to receive 1 of the 2 treatments for a 12-week period. The primary efficacy end point was the BP normalization rate (ie, the percentage of patients with a sitting DBP ≤90 mm Hg) after 12 weeks of treatment. Secondary end points were as follows: (1) the responder rate (ie, the percentage of patients whose sitting DBP was reduced by ≥10 mm Hg from baseline or had a DBP ≤90 mm Hg after 12 weeks of treatment), (2) the percentage of patients with a DBP ≤85 mm Hg, and (3) changes in sitting SBP and DBP after 4, 8, and 12 weeks of treatment.Results: A total of 159 hypertensive patients (88 women, 71 men) were randomized to receive D + I (44 women, 36 men; mean [SD] age, 53 [¹¹] years) or L + H (44 women, 35 men; mean [SD] age, 55 [¹⁰] years). No significant between-group differences were found in any of the primary or secondary end points of the study. Both combinations induced a significant reduction in sitting DBP and SBP from baseline (P<0.001 for both groups at week 12), without significant differences between the groups. Five mild to moderate adverse drug reactions (ADRs) occurred in each treatment group. No patient dropped out of the study because of an ADR.Conclusion: This study showed no difference between D + I and L + H interms of antihypertensive efficacy or tolerability in patients with mild to moderate hypertension.     

立西普利和卡托普利对离体缺血再灌大鼠心脏的保护作用

本文研究了血管紧张素转移酶抑制剂立西普利(Lis)和卡托普利(Cap)对离体大鼠心脏缺血再灌引起损伤的保护作用。实验证明Lis 100nmol/L和Cap 200μmol/L能明显降低心肌组织中丙二醛(MDA)的含量,保护超氧化物歧化酶(SOD)的活性。此外,这两种转移酶抑制剂均能升高心肌组织中前列环素(PGI_2)和谷胱甘肽(GSH)的含量。表明它们对心肌缺血再灌损伤均具明显的保护作用。     

赖诺普利对Ⅱ型糖尿病合并高血压患者胰岛素敏感性的影响

目的　探讨赖诺普利对Ⅱ型糖尿病合并高血压患者胰岛素敏感性的影响。方法　 31例Ⅱ型糖尿病合并高血压患者 ,每日口服赖诺普利 ,于服药前及服药后 8周末分别检测血压 (BP)、空腹血糖 (FBG)和空腹血浆胰岛素 (INS)、并作口服葡萄糖耐量试验 ,同时测定血浆胰岛素。结果　赖诺普利治疗后血压及血糖水平均明显降低 (P <0 .0 1) ,胰岛素敏感指数增高 (P <0 .0 1)。结论　赖诺普利可降低Ⅱ型糖尿病合并高血压患者血压及血糖水平 ,显著提高胰岛素敏感性。     

Prevention of salt induced hypertension and fibrosis by angiotensin converting enzyme inhibitors in Dahl S rats

BACKGROUND AND PURPOSE: In Dahl S rats, high salt increases activity of the tissue renin-angiotensin-aldosterone system (RAAS) in the CNS, heart and kidneys. Here, we assessed the effects of chronic angiotensin converting enzyme (ACE) inhibition on salt-induced hypertension and cardiovascular and renal hypertrophy and fibrosis, relative to the extent of ACE blockade. EXPERIMENTAL APPROACH: From 4.5 weeks of age, Dahl S rats received either the lipophilic ACE inhibitor trandolapril (1 or 5 mg kg(-1) day(-1)) or the hydrophilic ACE inhibitor lisinopril (10 or 50 mg kg(-1) day(-1)) and a high salt diet was started 0.5 week later. Treatments ended at 9 weeks of age. KEY RESULTS: High salt diet markedly increased blood pressure (BP), decreased plasma angiotensin II and increased ACE binding densities in brain, heart, aorta and kidneys. Trandolapril and lisinopril prevented 50% of the increase in BP in light and dark period of the day. After the last doses, trandolapril decreased ACE densities by approximately 80% in brain nuclei and heart and lisinopril by approximately 60% in the brain and by approximately 70% in the heart. The two ACE inhibitors prevented right ventricular hypertrophy and attenuated left ventricular hypertrophy but did not affect renal hypertrophy caused by high salt. Both drugs prevented high salt-induced fibrosis in heart, kidney and aorta. CONCLUSION AND IMPLICATION: As the ACE inhibitors could completely prevent tissue fibrosis and partially prevent tissue hypertrophy and hypertension, the tissue RAAS may play a critical role in salt-induced fibrosis, but a lesser role in the hypertrophy.     

Penile angioedema developing after 3 years of ACEI therapy

Background

Angiotensin-converting enzyme inhibitor−related angioedema (ACEI-RA) is a well-described condition, yet isolated genital ACEI-RA is a little-known entity.

Objective

A case of isolated genital angioedema is presented with photographic documentation. Possible complications and therapeutic options are discussed.

Case Report

A 71-year-old man presented with painless, nonpruritic genital swelling of 4 h duration. Medical history included peptic ulcer disease, hypertension, and benign prostatic hypertrophy. His medications included pantoprazole, hydrochlorothiazide, and lisinopril, which he had been taking for 3 years without any recent change in dosing. He was otherwise asymptomatic and previously had been in good health generally. The physical examination was positive only for diffuse, soft, nonpitting edema isolated to the scrotum and uncircumcised penis. The foreskin was only partially retractable. Urinalysis was normal. All symptoms resolved without complications within 48 h of discontinuing lisinopril and had not recurred at follow-up 4 months later. All cases of ACEI-RA isolated to the genitals that have been reported in the literature resolved without complications.

Conclusions

ACEI-RA can present as isolated swelling of the genitals and is a potential cause of genital swelling. Patients who have no evidence of airway compromise, paraphimosis, or urinary retention from complications such as phimosis can be safely discharged with instructions to discontinue the offending agent and to return in case of development of the aforementioned conditions.     

The effect of diminazene,an angiotensin-converting enzyme 2 activator,on adenine-induced chronic kidney disease in rats

The present study investigated the effect of diminazene, lisinopril, or valsartan on adenine-induced chronic kidney disease (CKD) in rats. The animals were divided into five groups (n = 6). The first and second groups received normal diet and adenine in the feed at a dose of 0.25% w/w for 35 days, respectively. The third, fourth, and fifth groups were treated as the second group but also received diminazene (15 mg/kg/day), lisinopril (10 mg/kg/day), and valsartan (30 mg/kg/day), respectively, for 35 days. Adenine significantly increased plasma urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), calcium, phosphorus, and uric acid. In addition, adenine increased urinary albumin/creatinine ratio and N-Acetyl-β-D-glucosaminidase (NAG)/creatinine ratio and reduced creatinine clearance. Adenine also significantly increased the plasma concentrations of inflammatory cytokines (plasma tumor necrosis factor–alpha [TNF-α] and interleukin-1beta [IL-1β]) and significantly reduced antioxidant indices (catalase, glutathione reductase [GR], and superoxide dismutase [SOD]). Histopathologically, renal tissue from adenine-treated rats showed necrosis of renal tubules, tubular casts, shrunken glomeruli, and increased renal fibrosis. All drugs ameliorated adenine-induced biochemical and histopathological changes. The protective effect of the three drugs used is, at least partially, due to their anti-inflammatory and antioxidant effects. Our results show that administration of diminazene, lisinopril, or valsartan had a comparable effect on the reversal of the biochemical and histopathological indices of adenine-induced CKD in rats.     

Acute and chronic effects of angiotensin converting enzyme inhibitors on the essential hypertensive kidney

Summary The natural course of essential hypertensive renal disease is characterized by a slowly progressive impairment of renal function. Initially, the changes are functional and reversible; however, structural changes gradually occur, leading to hypertensive nephrosclerosis. Similarities exist between the early functional hemodynamic changes observed in the essential hypertensive kidney and the physiologic renal effects of angiotensin II. To the degree that the initial functional changes are the result of excessive endogenous production of angiotensin II, interruption of the integrity of this humoral system could be expected to reverse the pathophysiologic sequence of events leading to hypertensive nephrosclerosis.This review focuses on the pathophysiology of the essential hypertensive kidney, the intrarenal effects of angiotensin II, and the acute and chronic effects of angiotensin converting enzyme (ACE) inhibition therapy on the essential hypertensive kidney. The data reviewed suggest that ACE inhibition therapy does reverse the initial functional hemodynamic changes observed in the essential hypertensive kidney and may protect the glomerulus from hemodynamically mediated injury