缬沙坦与西拉普利治疗老年单纯收缩期高血压临床对比观察

目的：观察缬沙坦与西拉普利分别联用小剂量双氢克尿噻对老年单纯收缩期高血压（ISH）患者的降压效果及血清代谢指标、左心室肥厚（LVH）的影响。方法：68例老年ISH患者随机分为2组，缬沙坦组34例，每天口服80～160mg缬沙坦＋12．5mg双氢克尿噻；西拉普利组34例．每天口服2．5～5mg西拉普利＋12．5mg双氢克尿噻；2组治疗前及治疗6个月后均行24小时动态血压监测（24h—ABPM）、心脏超声检查以及血清代谢指标测定，并对2组各指标进行了比较。结果：（1）不良反应：缬沙坦组胃部不适2例（6．06％），头昏1例（3．03％）；西拉普利组干咳6例（17．65％）。（2）2组治疗后的24小时平均收缩压（24h—SBP）、白天平均收缩压（d—SBP）和夜间平均收缩压（n-sBP）均较治疗前明显下降（P〈0．01）；2组组间治疗后各项血压指标相比差异均无统计学意义（P〉0．05）。（3）2组治疗前后的平均心率比较差异无统计学意义（P〉0．05）。（4）2组治疗后的左室重量指数（LVMl）均明显低于治疗前（P〈0．01）。（5）2组的空腹血糖（FBG）及血清钾（K^＋）、肌酐（SCr）、尿酸（UA）、总胆固醇（TC）、甘油三酯（TG）水平治疗前后比较差异均无统计学意义（P〉0．05）。结论：缬沙坦与西拉普利分别联用小剂量双氢克尿噻均能够较好地降低老年ISH患者的收缩压．对伴发的LVH均有消退作用。     

缬沙坦对Thy-1肾炎大鼠肾小球系膜细胞P27表达的影响

目的　观察Thy 1肾炎大鼠系膜细胞增生及P2 7表达 ,以及血管紧张素Ⅱ受体拮抗剂缬沙坦对其干预作用。方法　设正常组、Thy 1肾炎组及Thy 1肾炎 +缬沙坦治疗组。分别于各组疾病诱导后第 1、3、5、7d取肾脏行病理检查 ,免疫组化检测肾小球内PCNA、P2 7蛋白的表达 ,Westernblot分析肾小球内P2 7的表达。结果　在正常大鼠系膜细胞P2 7存在高表达 ,而在肾炎大鼠随系膜细胞增生 ,其P2 7表达减少。缬沙坦治疗组第 3～ 7d肾小球系膜细胞增生、系膜区扩张程度以及肾小球内PCNA表达低于肾炎组 (P <0 .0 5 ) ,而肾小球内P2 7表达高于肾炎组相应时间点 (P <0 .0 5 )。结论　肾小球系膜细胞非增殖状态的维系与其P2 7的高表达相关 ,缬沙坦可维持系膜细胞P2 7的高表达 ,抑制系膜细胞增殖及系膜扩张。提示缬沙坦对Thy 1肾炎大鼠有一定治疗作用     

缬沙坦对实验性肾病肾组织内皮素及其受体基因表达的影响

目的 观察血管紧张素受体拮抗剂缬沙坦(valsartan)对阿霉素肾病大鼠血浆及肾组织内皮素含量以及肾组织内皮素受体基因表达的影响。方法 SD大鼠经阿霉素诱导建立肾病综合征模型，设肾病模型组、valsartan治疗组、苯那普利(benazepril)治疗组及正常对照组。28天后比较各组大鼠间血浆及肾组织内皮素含量；应用RT-PCR技术检测大鼠肾组织内皮素-1(ET-1)及其A、B两型受体基因表达情况。结果 肾病综合征大鼠ET-1水平明显增加，肾脏内皮素A型受体表达显著增多；valsartan及benazepril治疗可使ET-A型受体表达明显下降，4组ET-B型受体mRNA表达无显著差异。结论 在肾病综合征状态下内皮素系统活性明显增强，血管紧张素受体拮抗剂valsaxtan可下调ET-A型受体mRNA表达，减轻ET-1在肾病综合征发生、发展中的作用。     

Redefining efficacy of antihypertensive therapies beyond blood pressure reduction--the role of angiotensin II antagonists

Antihypertensive efficacy must be redefined beyond blood pressure (BP) lowering per se to include reducing the cardiovascular complications of hypertension. Treatment decisions should be based on results from large clinical trials with relevant clinical outcomes. Several recent morbidity and mortality trials with angiotensin II receptor antagonists (AIIAs) provide an evidence-based rationale for the use of AIIAs in patients with hypertension. Studies with AIIAs in comparison to conventional antihypertensive agents showed improved morbidity and mortality outcomes in patients with hypertension and left ventricular hypertrophy (losartan) and diabetes mellitus (losartan and irbesartan). Trials with some members of the AIIA class (candesartan and valsartan) have not demonstrated such benefits in comparison to conventional agents, possibly due to differences in BP control during the trials. The results of these AIIA outcome trials have impacted on recently issued clinical guidelines for management of hypertension.     

Effects of glitazones on blood pressure and vascular structure in mesenteric resistance arteries and basilar artery from genetically hypertensive rats

1. The effects of two of the glitazone (thiazolidinedione) class of drugs, namely rosiglitazone and pioglitazone, on blood pressure and vascular remodelling in the New Zealand genetically hypertensive (GH) rat model were investigated. 2. In the first study, a GH group given rosiglitazone (5 mg/kg per day) from the age of 7 to 12 weeks was compared with a GH control group. In the second study, GH rats were given either pioglitazone, simvastatin, valsartan or combinations of pioglitazone with simvastatin or valsartan (all drugs at a dose of 10 mg/kg per day). 3. Tail-cuff systolic blood pressure was measured weekly. At the end of the experiment, blood vessels were fixed by perfusion and samples of mesenteric resistance arteries (MRA), second-order branches and basilar artery were embedded in Technovit and serial sections were cut and stained with Giemsa for stereological analysis. Media width, medial cross-sectional area and lumen diameter were determined and the ratio of media width/lumen diameter was calculated. 4. Rosiglitazone significantly reduced blood pressure in GH rats. 5. In MRA, rosiglitazone had a hypotrophic effect on media, reduced lumen diameter and reduced media/lumen ratio (P<0.001). 6. In basilar artery, there was also a hypotrophic effect of rosiglitazone on media and reduced media/lumen ratio (P<0.001). 7. Pioglitazone slowed down the rate of blood pressure increase with age in GH rats and had a greater effect on blood pressure when given in combination with simvastatin. 8. Pioglitazone had a hypotrophic effect on the media of MRA and basilar artery. The hypotrophic effect was enhanced when pioglitazone was given in combination with simvastatin. The media/lumen ratio was reduced by pioglitazone; in MRA, combination treatment with simvastatin reduced the ratio further to normal and, with valsartan, to below normal. In basilar artery, the media/lumen ratio was reduced further by both combination treatments, but was lowest in the pioglitazone-valsartan combination group. 9. The significant effects on MRA and basilar artery structure (and, thus, haemodynamics) seen after rosiglitazone monotherapy and after pioglitazone, given alone and in combination with simvastatin or valsartan, may well indicate a glitazone class effect on vascular structure and, hence, cardiovascular function.     

Effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the genetically hypertensive rat model

1. The aims of the present study were to investigate, in the New Zealand genetically hypertensive (GH) rat model, the effects of treatment with simvastatin, alone or in combination with valsartan or enalapril, on blood pressure (BP) and structural remodelling of mesenteric resistance arteries (MRA) and of the basilar artery, an artery that plays a major role in the regulation of cerebral resistance. 2. Genetically hypertensive rats were treated with simvastatin at two dose levels (5 and 10 mg/kg per day) and simvastatin in combination with valsartan or enalapril (also 5 and 10 mg/kg per day) from the age of 7 to 12 weeks. Systolic BP and bodyweight were measured weekly. 3. At the end of the experiment, following fixation by perfusion, MRA and the basilar artery were excised and embedded in Technovit (a glycol methacrylate medium; Heraeus Kulzer, Werheim, Germany). Serial sections were cut and stereological techniques used to determine tunica media width and cross-sectional area (CSA), lumen diameter and the ratio of media width/lumen diameter. 4. Simvastatin monotherapy did not lower BP at either dose. In the high- and low-dose groups, the combination of simvastatin + enalapril lowered BP more than with enalapril alone; this was also true for the simvastatin + valsartan combination in the lower-dose group. 5. The MRA were hypotrophically remodelled by the 10 mg/kg per day dose of simvastatin; the 5 mg/kg per day dose caused hypotrophic remodelling with decreased media/lumen ratio. Valsartan and enalapril caused hypotrophic remodelling together with outward remodelling of the lumen in the 10 mg/kg per day valsartan group and, in all groups, a reduction in the media/lumen ratio, with the greatest effect observed in the high-dose groups. 6. The combination treatments of simvastatin + valsartan and simvastatin + enalapril did not have any consistent extra effect on MRA remodelling. 7. In the basilar artery, high-dose simvastatin had a hypotrophic effect on the media and both doses reduced the media/lumen ratio independently of any change in BP. 8. Simvastatin given in combination with valsartan produced a slight further reduction in medial CSA, media width and ratio. In combination with enalapril, there was little consistent additional effect. 9. Simvastatin monotherapy hypotrophically remodelled the media of the basilar artery in the GH rat model, even in the absence of changes in BP. A similar structural effect may explain, in part, the reduction in stroke seen in patients treated with statins.     

沙库巴曲缬沙坦对慢性心力衰竭合并肾功能不全患者容量管理的优化作用

[摘要] 目的 观察慢性心力衰竭（心衰）合并肾功能不全患者应用沙库巴曲缬沙坦后容量状态变化及其对心脏结构和功能的影响。方法 连续入选84例慢性心衰合并肾功能不全患者,分为沙库巴曲缬沙坦（ARNI）组48例和对照组36例。ARNI组接受沙库巴曲缬沙坦治疗,对照组接受单一的缬沙坦治疗。测量2组患者服药6个月后24小时尿量、利尿剂用量,检测血浆B型脑钠肽（BNP）水平,随访纽约心脏病协会（NYHA）分级变化,并以超声心动图评价心脏结构及功能的改善情况。结果 （1）两组患者基线临床资料差异均无统计学意义（P?0.05）。（2）ARNI组服药后与对照组比较,患者24小时尿量明显增多（P<0.01）;NYHA分级明显改善（P=0.032）。ARNI组服药后与服药前比较,患者服用利尿剂剂量、BNP水平明显降低（P均<0.01）;24小时尿量明显增加（P<0.01）。（3）ARNI组服药后与对照组比较,患者每搏输出量（SV）、心输出量（CO）、左室射血分数（LVEF）、二尖瓣环E峰与A峰比值（E/A）明显升高（P均<0.05）,左房内径（LA）缩小（P<0.05）;ARNI组服药后与服药前比较,患者左室舒张末内径（LVDD）、左室收缩末内径（LVSD）、LA明显缩小（P均<0.01）;SV、CO、E/A、LVEF明显升高（P均<0.01）。结论 与单一使用缬沙坦比较,沙库巴曲缬沙坦可明显改善合并肾功能不全的慢性心衰患者的容量超负荷,优化容量管理措施,超声心动图证实了其对心脏收缩及舒张功能的改善。     

丹参川芎嗪注射液联合缬沙坦治疗早期糖尿病肾病的临床观察

目的探讨丹参川芎嗪注射液联合缬沙坦治疗早期糖尿病肾病临床疗效。方法选择糖尿病肾病Ⅲ期78例患者,随机分观察组39例和对照组39例。对照组给缬沙坦80 mg,1次/d,共4周。观察组在应用缬沙坦的基础上,加用丹参川芎嗪注射液10 mL+生理盐水250 mL静滴,1次/d,共4周。结果观察组与对照组治疗后血肌酐24 h尿蛋白定量、糖化血红蛋白、收缩压、舒张压,治疗前后比较差异有统计学意义(P<0.05),组间差异亦有统计学意义(P<0.05)。结论丹参川芎嗪注射液联合缬沙坦治疗早期糖尿病肾病疗效优于对照组,且无明显不良反应。     

缬沙坦胶囊、厄贝沙坦片治疗糖尿病肾病患者106例临床观察

目的前瞻性观察缬沙坦与厄贝沙坦对糖尿病肾病患者微量尿白蛋白及血压的影响。方法前瞻性观察106例2型糖尿病肾病患者,按数字表法将患者随机分为A、B两组,均采用相应的基础降糖治疗后,A组(n=51)患者加用缬沙坦80 mg/d,B组患者(n=55)用厄贝沙坦150 mg/d,12周为1个疗程,每疗程观察微量白蛋白尿及血压,共3个疗程。结果①缬沙坦及厄贝沙坦对微量尿白蛋白经3个疗程治疗后,差异有统计学意义(Z=-6.490,P<0.001)。两种药物对于微量尿白蛋白治疗在各疗程终点比较差异无统计学意义(P>0.05)。②缬沙坦及厄贝沙坦对血压经3个疗程治疗后差异有统计学意义(P<0.05)。两种药物对于收缩压治疗在各疗程终点比较,差异有统计学意义(P<0.05)。结论两组药物均有减少糖尿病肾病患者微量蛋白尿及降压作用,而厄贝沙坦比缬沙坦在降低血压方面更有优势。     

缬沙坦对70岁以上高血压患者合并蛋白尿疗效观察

目的观察不同降压药物对≥70岁高血压患者合并蛋白尿的治疗效果。方法 78例≥70岁高血压合并蛋白尿患者,停用原用药1周,血压明显增高者,临时加用短效利尿剂,随机均分为2组。A组口服硝苯地平缓释片10mg,每天2次;B组口服缬沙坦胶囊80mg,每天1次。疗程12周,每天监测血压2次,并记录出现的不良反应。用药前后测尿微量白蛋白（MAU）,血、尿β2微球蛋白,血肌酐、血常规和肝功能。结果治疗12周后2组血压均下降,总有效率无显著差异。B组尿微量白蛋白和血、尿β2微球蛋白浓度均显著下降（P〈0.05）,A组尿微量白蛋白,血、尿β2微球蛋白无明显下降,2组间有显著性差异（P〈0.01）。结论缬沙坦在有效降血压的同时,可显著降低尿中微量白蛋白及血、尿β2微球蛋白。