金水宝联合缬沙坦治疗2型糖尿病肾病的早期疗效

目的：观察金水宝联合缬沙坦对尿微量白蛋白排泄率及尿白蛋白/肌酐比值的影响,探讨其对糖尿病肾病的早期保护。方法：90例2型糖尿病早期肾病患者,随机分成常规对照组、缬沙坦组、金水宝联合缬沙坦组,经6个月治疗后,观察尿白蛋白排泄率和尿白蛋白/肌酐比值的变化,评价金水宝联合缬沙坦的肾脏保护作用。结果：缬沙坦组尿白蛋白排泄率和尿白蛋白/肌酐比值较常规对照组都有下降（P〈0.05）;金水宝联合缬沙坦组下降更加明显,达到了统计学显著性差异（P〈0.01）,与缬沙坦组相比也有差异（P〈0.05）。结论：金水宝联合缬沙坦降低尿白蛋白排泄率和尿白蛋白/肌酐比值较单用缬沙坦更明显。     

缬沙坦对大鼠心肌梗死后心室重构的影响

目的:探讨缬沙坦对大鼠心肌梗死(MI)后心室重构和左室非梗死区(LVNIZ)心肌血管紧张素Ⅱ(AngⅡ)及醛固酮(Ald)的影响。方法:选取雌性Wistar大鼠结扎左冠状动脉,建立MI模型。术后将存活大鼠随机分为缬沙坦组给予缬沙坦15mg·kg-·1d-1直接灌胃给药,另设MI组、假手术组分别灌等量自来水,连续4周。心脏标本病理分析,测定左室截面直径(LVTD),VG染色测定LVNIZ的胶原容积分数(CVF),放免法测定LVNIZ的AngⅡ、Ald含量。结果:与假手术组比较,MI组LVTD(P<0.01)、CVF(P<0.01)、AngⅡ(P<0.05)及Ald(P<0.01)含量均显著增加;缬沙坦使增加的LVTD(P<0.05)、CVF(P<0.05)、AngⅡ(P<0.05)、Ald(P<0.01)显著降低。结论:缬沙坦可能通过抑制心肌局部AngⅡ及Ald的过表达而逆转心室重构。     

国产复方缬沙坦治疗轻中度高血压的临床疗效

目的:评价国产缬沙坦80 mg/氢氯噻嗪12．5 mg复方制剂(复方缬沙坦)治疗原发性轻中度高血压的临床疗效。方法:采用随机、单盲、自身对照的多中心研究,入选轻中度原发性高血压患者222例,年龄18～69岁,坐位舒张压(SeDBP)95～114 mmHg和坐位收缩压(SeSBP)＜180 mmHg,不伴有严重的靶器官损害。经2周洗脱期后,全部口服单剂缬沙坦80 mg·d~(-1),qd,服用2周后血压作为观察基线值,未达标者改服复方缬沙坦(80 mg/12．5 mg．qd),服药6周后与自身基线值比较,评价其疗效及安全性。结果:112例患者完成了6周的复方缬沙坦治疗,6周后平均坐位舒张压和收缩压分别下降了(10．04±7．34)mmHg和(14．18±11．83)mmHg,治疗有效率为76．8%(86/112例)。结论:复方缬沙坦治疗国人轻中度原发性高血压安全有效,可维持24 h平稳降压。     

缬沙坦对高血压及心率变异性影响的研究

目的:研究缬沙坦对高血压心率变异性的影响。方法:选择80例原发性高血压患者服用缬沙坦,分别在治疗前与治疗14周后进行动态心电图(DCG)及心率变异性(HRV)检查,并与对照组(40例)进行比较。结果:治疗后连续R-R间期标准差(SDNN),相邻R-R均方差(RMSSD),相邻R-R间期大于50ms百分数(PNN50)、高频功率(HF)值均明显上升;低频功率与高频功率比值(LF/HF)显著降低(P<0.01),结论:原发性高血压患者存在HRV下降,而缬沙坦在降压的同时,可提高HRV,改善自主神经功能失调。     

缬沙坦治疗慢性移植肾肾病临床观察

目的:观察缬沙坦治疗慢性移植肾肾病(CAN)的有效性及安全性。方法:将72例CAN患者分两组:治疗组41例予缬沙坦治疗,平均治疗(3 6.0±7.2 )个月;对照组3 1例不予缬沙坦治疗。动态观察患者血肌酐(SCr)变化以及血压、血红蛋白、2 4h尿蛋白定量等指标。结果:经过3 6、3 4个月的随访,两组患者分别有7例(17.1% )和11例(3 5 .5 % )发生初级终点事件,即SCr上升≥5 0 % (P =0 .10 ) ;治疗组联合终点事件(指患者死亡或返回透析)的发生率显著低于对照组(分别为9.8%和3 8.7% ,P <0 .0 1) ;且治疗组达到联合终点的时间也显著长于对照组(分别为5 3 .9个月和41.5个月,P =0 .0 2 )。治疗组患者尿蛋白排泄量明显降低(P =0 .0 13 )。缬沙坦治疗的常见副作用是高钾血症和贫血。结论:缬沙坦治疗可有效降低移植肾功能丧失发生率,延缓移植肾功能衰竭的进展。     

Valsartan与benazepril联合应用对自发性高血压大鼠血压和左心室肥厚的影响

目的:评价血管紧张素转换酶抑制剂苯那普利钠和AT_1受体拮抗剂缬沙坦联合应用对自发性高血压大鼠(SHR)的降压疗效及其逆转心肌肥厚作用和对肾素-血管紧张素-醛固酮系统(RAAS)、内洋地黄素水平的影响.方法:24只14周龄雄性SHR随机分成空白对照组、Benazepril组、Valsartan组和Benazepril Valsartan组,另设WKY正常对照组.分别于药物干预前、药物干预后2、4、6、8周末测定大鼠SBP;于药物干预后8周末检测心肌组织和血浆肾素活性、血管紧张素Ⅱ浓度、心肌组织Na~ -K~ -ATP酶活性和内洋地黄素水平,并行心肌组织形态学检查.结果:药物干预各组SHR动脉收缩压(SBP)水平明显下降,尤以联合用药组SBP下降最显著;药物干预各组血浆和心肌组织肾素活性均明显升高;Benazepril组和Benazepril Valsartan组血浆和心肌组织Ang Ⅱ水平降低,而Valsartan组血浆和心肌组织Ang Ⅱ水平则明显升高;随SBP水平的降低,心肌组织Na~ -K~ -ATP酶活性明显升高,而内洋地黄素水平则明显下降;药物干预各组LVM/BW、TDM均明显减低,尤以联合用药组改变最为显著.结论:ACEI Benazepril和AT_1拮抗剂Valsartan均有明显的降低SHR的SBP作用,能明显逆转左室肥厚;联合用药效果最为显著,并能有效防止单一AT_1拮抗剂所致血浆和心肌组织Ang Ⅱ水平的升高的副作     

缬沙坦治疗肾性高血压64例临床观察

目的观察缬沙坦对慢性肾病继发性高血压的治疗作用。方法对64例肾性高血压患者应用缬沙坦治疗8周,观测治疗前后的血压及血钾、钠、氯、24 h尿蛋白定量、血尿素氮(BUN)、肌酐(SCr)、血促红细胞生成素(Epo)等的变化。结果应用缬沙坦8周后,血钾、钠、氯、24 h时尿蛋白定量、BUN、SCr、Epo无明显变化(P>0.05);24 h尿蛋白定量减少(P<0.05)。结论缬沙坦在治疗慢性肾病继发性高血压的过程中对血钾、钠、氯、BUN、SCr及Epo无明显影响,使24 h尿蛋白定量明显减少。     

Effects of valsartan/ hydrochlorothiazide and amlodipine on ambulatory blood pressure and plasma norepinephrine levels in high-risk hypertensive patients

The efficacy and tolerability of the combination of valsartan and hydrochlorothi-azide (HCTZ) were compared with that of amlodipine in reducing ambulatory blood pressure and plasma norepinephrine levels in patients with mild to moderate hypertension and at least 1 cardiovascular risk factor. At the end of a 2-week washout period, 92 outpatients with a sitting diastolic blood pressure ≥95 and <110 mm Hg, associated with at least 1 additional risk factor, were randomly assigned to receive either valsartan 160 mg and HCTZ 12.5 mg once daily (n=46) or amlodipine 10 mg alone once daily (n=46) for 12 weeks, according to a prospective, randomized, open-label, blinded end point, parallel-group design. At the end of the washout period and after 6 and 12 weeks of active treatment, 24-hour ambulatory blood pressure monitoring was performed, and clinical blood pressure and heart rate and plasma norepinephrine levels were assessed (by high-performance liquid chromatography). Both the valsartan/HCTZ combination and amlodipine had a demonstrable antihypertensive effect, but the combination showed an antihypertensive effect significantly greater than that of amlodipine, as demonstrated by the 24-hour (P < .001), daytime (P < .001), and nighttime ambulatory blood pressure values (P < .01) and by the clinical blood pressure values at trough, which were all significantly lower. Although the trough-to-peak ratios were similar in both groups, the smoothness indexes pertaining to both systolic and diastolic pressures were significantly higher (P < .05 andP < .001, respectively) in patients receiving valsartan/HCTZ, suggesting the combination produces a more homogeneous antihypertensive effect. A significant increase in plasma norepinephrine levels was associated with amlodipine (+9% at 6 weeks, +15% at 12 weeks) but not with the valsartan/HCTZ combination. The valsartan/HCTZ combination was better tolerated than amlodipine, which was associated with a higher frequency of ankle edema. These results indicate that the combination of valsartan 160 mg and HCTZ 12.5 mg provides more sustained and homogeneous control of blood pressure than does amlodipine 10 mg in high-risk hypertensive patients, without producing reflex sympathetic activation.     

Podocyte foot process broadening in experimental diabetic nephropathy: amelioration with renin-angiotensin blockade

Aims/hypothesis. Changes in podocyte number and morphology have been implicated in the pathogenesis of proteinuria and the progression of human and experimental kidney disease. This study sought to examine podocyte foot process and slit pore architecture in experimental diabetic nephropathy and to determine whether such changes were modified with renoprotective intervention by blockade of the renin-angiotensin system. Methods. The number of filtration slits per 100 μm of glomerular basement membrane was assessed by transmission electron microscopy and quantitated histomorphometrically in control animals and in rats with 24 weeks of streptozotocin-induced diabetes. Diabetic rats were either untreated or received the angiotensin converting enzyme inhibitor ramipril, or the angiotensin II type 1 receptor antagonist, valsartan. Results. When compared with control animals, diabetes was associated with a decrease in the number of slit pores per unit length of glomerular basement membrane, indicative of podocyte foot process broadening. Both ramipril and valsartan attenuated these ultrastructural changes to a similar degree. These differences remained after correcting for glomerular volume as a possible confounding variable. Conclusion/interpretation. Preservation of podocyte architecture could contribute to the renoprotective effects of renin-angiotensin system blockade in diabetic nephropathy. [Diabetologia (2001) 44: 878–882] Received: 19 January 2001 and in revised form: 28 March 2001     

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.