缬沙坦长期治疗对原发性高血压患者左心室肥厚及心功能影响的对比研究

目的探讨血管紧张素Ⅱ受体拮抗剂--缬沙坦对原发性高血压患者左心室肥厚及心功能的影响.方法入选经超声心动图检查证实为原发性高血压的左心室肥厚患者72例,随机分配到缬沙坦组(口服80～160mg/d)或阿替洛尔组(口服25～50 mg/d)(n均=36),治疗8个月,治疗前后各检查一次超声心动图及放射性核素心室显像,对比分析组内治疗前后左心室重量指数及左心功能参数变化和两组间的差异.结果①与治疗前比较,原发性高血压患者在缬沙坦或阿替洛尔治疗8个月后,两组收缩压与舒张压明显下降(159/101 mmHg至142/89 mmHg;161/103 mmHg至145/90mmHg,1 mmHg=0.133 kPa)(P均＜0.01).②原发性高血压患者在缬沙坦治疗8个月后,左心室后壁与室间隔厚度较治疗前显著下降(P均＜0.05),左心室重量及左心室重量指数下降更显著(P均＜0.01);而在阿替洛尔治疗8个月后左心室后壁与室间隔厚度无明显变化,左心室重量及左心室重量指数下降显著(P＜0.05).③原发性高血压患者在缬沙坦治疗8个月后左心室高峰充盈率明显增加(P＜0.05),而在阿替洛尔治疗8个月后左心室高峰充盈率无明显变化,两组间比较则有明显差别(P＜0.05).结论原发性高血压患者在缬沙坦治疗8个月后可使原发性高血压患者左心室肥厚显著逆转及左心室舒张功能显著改善,缬沙坦对左心室舒张功能的作用优于阿替洛尔.     

Effect of insulin-sensitizing agents in combination with ezetimibe, and valsartan in rats with non-alcoholic fatty liver disease

AIM: To assess whether treatment with insulin-sensitizing agents (ISAs) in combination with ezetimibe and valsartan have greater effect on hepatic fat content and lipid peroxidation compared to monotherapy in the methionine choline-deficient diet (MCDD) rat model of non-alcoholic fatty liver disease (NAFLD). METHODS: Rats (n = 6 per group) were treated with different drugs, including MCDD only, MCDD diet with either metformin (200 mg/kg), rosiglitazone (3 mg/kg), metformin plus rosiglitazone (M R), ezetimibe (2 mg/ kg), valsartan (2 mg/kg), or combination of all drugs for a total of 15 wk. Liver histology, lipids, parameters of oxidative stress and TNF-alpha were measured. RESULTS: Fatty liver (FL) rats demonstrated severe hepatic fatty infiltration (> 91% fat), with an increase in hepatic TG ( 1263%, P < 0.001), hepatic cholesterol ( 245%, P < 0.03), hepatic MDA levels ( 225%, P < 0.001), serum TNF-alpha (17.8±10 vs 7.8±0.0, P < 0.001), but a decrease in hepatic alpha tocopherol (-74%, P < 0.001) as compared to the control rats. Combination therapy with all drugs produced a significant decrease in liver steatosis (-54%), hepatic TG (-64%), hepatic cholesterol (-31%) and hepatic MDA (-70%), but increased hepatic alpha tocopherol ( 443%) as compared to FL rats. Combination therapy with ISA alone produced a smaller decrease in liver steatosis (-32% vs -54%, P < 0.001) and in hepatic MDA levels (-55% vs -70%, P < 0.01), but a similar decrease in hepatic lipids when compared with the all drugs combination. TNF-alpha levels decreased significantly in all treatment groups except in ISA group. CONCLUSION: Combination therapies have a greater effect on liver fat content as compared to monotherapy. Rosiglitazone appears to improve hepatic steatosis to a greater extent than metformin.     

缬沙坦和卡托普利干预高血压大鼠左室心肌纤维化及超微结构改变的比较研究

目的：比较缬沙坦和卡托普利对心肌纤维化及超微结构改变的干预作用。方法：14周龄自发性高血压大鼠(SHR)25只随机分为5组：缬沙坦组(SHRv)、卡托普利组(SHRc)、卡托普利组 缬沙坦组(SHRc v)、假治对照组(SHR20)和高血压基础对照组(SHR14)。同周龄SD大鼠5只设为正常对照组(SD20)。疗程为6周。处死后测算左室重量／体重比(LVM／BW)、光镜观察心肌胶原分布，测算胶原容积分数(CVF)、血管周围胶原面积／管腔面积比(PVCA／LA)和组织匀浆胶原浓度，电镜观察心肌超微结构改变。结果：三个治疗组反映心肌纤维化的多项指标均较SHR20和SHR14组显著改善(P＜0．0l＆0．05)。SHRv与SHRc v组的改善相似，均优于SHRc组(P＜0．05)，但仍差于SD20组(P＜0．05)。心肌超微结构改变均较SHR20组显著好转。结论：缬沙坦和卡托普利均能抑制高血压心肌纤维化及超微结构改变，但短期治疗不能恢复正常。缬沙坦的作用优于卡托普利，两者联用优于单用卡托普利，但并不显著优于单用缬沙坦。     

缬沙坦对阿霉素致心肌损伤大鼠心肌结构改变的影响

目的研究缬沙坦对阿霉素(adriamycin,ADR)致大鼠心功能损伤及心肌结构改变的保护作用。方法大鼠腹腔注射ADR(20mg/kg)造成心脏损伤模型。观察缬沙坦对ADR致心肌损伤大鼠体重、左心室功能、血清超氧化物歧化酶(SOD)、肌酸激酶同工酶(CK-MB)和丙二醛(MDA)的变化。结果①ADR组大鼠血清CK-MB活性和MDA含量及左心室舒张末期压(LVEDP)较对照组明显增加;血清SOD、左心室收缩压(LVSP)、左心室等容收缩期压力变化速率最大值( dp/dtmax)显著降低;电镜下可见,ADR组大鼠心肌细胞严重损伤,心肌纤维溶解,肌质网扩张空泡化,线粒体水肿,嵴断裂。②缬沙坦 阿霉素组大鼠CK-MB活性和MDA含量及LVEDP显著降低;SOD和 dp/dtmax显著升高;电镜下可见,局灶性的心肌细胞肌浆溶解;散在性的心肌细胞空泡样变。结论缬沙坦可减轻自由基对心脏的损伤,改善ADR致心肌损伤的毒性反应,并能有效地防治心功能损伤。     

缬沙坦或吲达帕胺对中青年男性高血压患者性功能影响

目的　探讨缬沙坦和吲达帕胺对中青年男性高血压患者降压的疗效以及对性功能的影响。方法　将入选的 12 0例患者随机分为两组 ,一组服用缬沙坦 ,另一组服用吲达帕胺 ,观察治疗 8周前后血压及性功能变化。结果　缬沙坦和吲达帕胺均能显著降压 (P <0 0 1)。缬沙坦治疗后明显增加了勃起功能指数 (17.7± 4 6vs 14± 5 6 ,P <0 0 1)和每周性交次数 (3 2± 1 2次 /周vs 2 2±1 1次 /周 ) ,两者差异显著 (P <0 0 1) ;而吲达帕胺治疗前后患者性功能无明显改变 (P >0 0 5 )。结论　缬沙坦在降压的同时能显著改善男性性功能。     

缬沙坦改善原发性高血压患者血管内皮功能

目的探讨缬沙坦对原发性高血压患者血管内皮功能的影响。方法36例原发性高血压患者口服缬沙坦80mg,1次/d。治疗8周前后,采用高分辨血管外超声法测定治疗前后肱动脉内皮依赖性血管舒张功能;采用硝酸还原法测定血清一氧化氮(NO),化学比色法测定血清超氧化物岐化酶(SOD)及丙二醛(MDA)即脂质过氧化物(LPO)浓度。选择26例正常人作为对照组。结果治疗前反应性充血引起的肱动脉变化与正常对照组比较明显减弱P<0.01,治疗后明显改善P<0.01。服用缬沙坦前与正常对照组的NO水平比较P<0.01,治疗后与治疗前相比较具有明显的提高P<0.01。治疗前与对照组相比SOD活性较对照组明显降低(P<0.01),MDA活性明显增高(P<0.01),经缬沙坦治疗后SOD活性较治疗前明显增高(P<0.01),MDA活性明显降低(P<0.01)。单因素相关分析显示:原发性高血压患者在进行缬沙坦治疗后反应性充血时肱动脉内径的变化与NO水平呈线性正相关P<0.01,r=0.798。结论缬沙坦可改善血管内皮依赖性舒张功能,减少氧化应激。     

缬沙坦对原发性高血压病人血管内皮功能的影响

目的探讨缬沙坦对原发性高血压（EH）病人血管内皮功能的影响。方法检测应用缬沙坦治疗前后EH病人血压、血管内皮素-1（ET1）及一氧化氮（NO）的变化，并进行分析。结果应用缬沙坦后。EH病人血压显著下降（P〈0．01）、ET-1明显降低（P〈0．01），NO明显升高（P〈0．01）。结论缬沙坦可有效降压。并能逆转EH病人血管内皮功能紊乱。     

缬沙坦对过氧化氢损伤乳鼠心肌细胞的保护作用

目的探讨缬沙坦对过氧化氢（H2O2）致心肌细胞氧化损伤的保护作用及其机制。方法用H2O2作用于新生SD大鼠心肌细胞,建立心肌细胞H2O2损伤模型。用缬沙坦预处理后,观察心肌细胞结构,测定心肌细胞存活率、乳酸脱氢酶（LDH）、丙二醛（MDA）及一氧化氮（NO）水平。结果缬沙坦提高心肌细胞过氧化损伤的细胞存活率（P〈0.05）,减少损伤时LDH、MDA和NO的生成（P〈0.05）。结论缬沙坦通过抗氧化、抗脂质过氧化反应,对心肌细胞过氧化损伤起保护作用。     

Effects of AT1 Antagonist on MMP2, MMP9 Expression and Collagen Remodeling in Left Ventricle of Rabbit Undergoing Chronic Pressure Overload

Objectives To study the effects of AT1 antagonist on MMP2, MMP9 expression and collagen remodeling in left ventricle of rabbit undergoing chronic pressure overload. Methods 30 rabbits were randomly divided into 3 groups (n= 10,each group), including sham operation group, abdominal aorta banded group(banded group), abdominal aorta banded valsartan group (valsartan group).Twelve weeks after operation,hemodynamic parame-ters were acquired, then collagen volume fraction(CVF) and MMP2, MMP9 expression of left ventricle were measured by using VG and immunohistochemical stain. Results Compared with sham operation group, both MMP2 and MMP9 expression were enhanced in banded group; meanwhile, LVW/BW,LVEDP and CVF increased significantly. Compared with banded group, both MMP2 and MMP9 expression were weakened in valarstan group; simultaneously,LVW/BW, LVEDP and CVF decreased significantly.Conclusions Expression of MMP2 and MMP9 was enhanced in left ventricle of rabbit undergoing chronic pressure overload, which may be associated with collagen proliferation, ventricule remodeling and impaired heart function; Valsartan could inhibit collagen proliferation, prevent ventricule remodeling and preserve heart function by inhibiting abnormal expression of MMP2 and MMP9.     

缬沙坦治疗原发性高血压对内源性纤溶活性的影响

目的 :观察缬沙坦治疗原发性高血压 (EH)的同时对内源性纤溶活性的影响。方法 :用发色底物分解显色法测定 6 4例EH患者 (EH组 )和 35例正常对照者 (对照组 )的组织型纤溶酶原激活因子 (t PA)、纤溶酶原激活抑制物 (PAI 1)的活性 ,然后EH组口服缬沙坦 80mg ,每日 1次 ,共 8周 ,比较治疗前后的t PA和PAI 1活性变化。结果 :EH组治疗前t PA活性较对照组明显降低 ,PAI 1活性明显升高 (P <0 .0 5 )。经缬沙坦治疗 8周后 ,t PA活性较治疗前显著上升 ,PAI 1活性降低 (P <0 .0 5 )。结论 :缬沙坦在降低血压的同时 ,有改善内源性纤溶活性的作用。