氯沙坦、福辛普利及硝苯地平控释剂对原发性高血压患者诊所血压及24小时动态血压作用之比较

目的探讨氯沙坦、福辛普利和硝苯地平控释剂对原发性高血压患者诊所血压及昼夜血压的影响,并进行比较.方法87例轻、中度原发性高血压患者随机分为3组,分别服用氯沙坦50?mg/d(L组,30例)、福辛普利10?mg/d(F组,28例)和硝苯地平控释剂30?mg/d(N组,29例),比较治疗前及治疗4周末对诊所血压(OBP)[BFQ、动态血压的影响.结果3组治疗4周末OBP、动态血压均较服药前降低,有显著性差异([WTBXP＜0.05～0.001),3组间无显著性差异;各组均能维持正常的血压昼夜节律,24小时血压谷/峰(T/P)均大于70%;以N组作用显著.各组不良反应发生率分别为F组39.4%、N组43.8%、L组18.2%,N组24小时平均心率较治疗前明显加快(P＜0.05).结论氯沙坦、福辛普利和硝苯地平控释剂均能有效持续降低血压.治疗后硝苯地平控释剂24小时血压谷/峰优于氯沙坦和福辛普利.氯沙坦服药后的耐受性优于福辛普利及硝苯地平控释剂.     

Peripheral artery disease and outcomes after myocardial infarction: An individual-patient meta-analysis of 28,771 patients in CAPRICORN,EPEHESUS, OPTIMAAL and VALIANT

Objectives

To examine the prevalence of peripheral artery disease (PAD) and the relationship between PAD and cardiovascular (CV) outcomes in subjects with left ventricular systolic dysfunction, heart failure or both after acute myocardial infarction (MI).

Background

PAD is associated with poorer prognosis in patients with stable and unstable coronary heart disease but whether PAD is associated with worse outcomes following substantial acute MI is unknown.

Methods

Univariate and multivariate Cox proportional hazards modelling was used to compare clinical outcomes in an individual-patient meta-analysis of 4 trials (CAPRICORN, EPHESUS, OPTIMAAL and VALIANT).

Results

Of the 28,771 patients randomized, 2357 (8.2%) had PAD. These patients were older and had more co-morbidity and were less likely to be prescribed aspirin or a beta-blocker compared to patients without PAD. Over a mean follow-up of 2.7 years, 5121 (17.8%) patients died and 15,055 (52.3%) experienced CV death or hospitalization. PAD was an independent predictor of all individual and composite CV outcomes examined (including heart failure), with the exception of stroke. In patients with PAD (compared to those without PAD), the adjusted hazard ratio (HR) for all-cause mortality was 1.25 (95% CI 1.15–1.37; p < 0.001) and the HR for CV death, non-fatal MI, non-fatal stroke or heart failure hospitalization was 1.24 (1.16–1.33; p < 0.001).

Conclusions

PAD is common and is an independent predictor of worse outcomes in patients already at high risk after MI because of left ventricular systolic dysfunction, heart failure or both. These patients represent an important group for intensive application of secondary preventive therapies.     

洛沙坦对心脏和动脉衰老保护作用的实验研究

目的观察老龄大鼠心肌纤维化程度、血管内皮依赖性舒张功能不全的变化及洛沙坦的干预作用,探讨血管紧张素II受体I(AT1R)拮抗剂(ARB)对心脏和动脉衰老的保护作用。方法Wistar大鼠30只,分为成年组、老龄组、洛沙坦组,生化法测心肌纤维化指标,免疫组化法测转化生长因子β1(TGFβ1)的表达。硝酸还原酶法测主动脉NO生成量,比色法测主动脉NOS活力。结果与成年组比较,老龄组心肌纤维化程度明显升高,TGFβ1表达上调,乙酰胆碱介导的内皮依赖性舒张反应受损(P<005),NO量及总NOS活力均显著降低(P<001)。与老龄组比较,洛沙坦组心肌纤维化程度明显降低(P<005),心肌TGFβ1表达减少,内皮依赖性舒张反应明显提高(P<001),NO量及总NOS活力均显著升高(P<005)。结论随着增龄,心肌纤维化程度增高,TGFβ1表达逐渐增加,血管内皮依赖性舒张功能减退。洛沙坦可抑制老龄大鼠心肌纤维化的形成,对增龄引起的血管内皮功能不良有改善作用。     

依普沙坦治疗原发性高血压的临床研究

目的 观察进口依普沙坦片治疗原发性高血压的疗效与安全性。方法 以氯沙坦钾片为对照，对连续的52例1～2级原发性高血压门诊患者进行8周的随机、双盲、双模拟、平行对照治疗观察。结果 治疗8周后，依普沙坦片的降压幅度为（20±15））／（18±9）mmHg（1mmHg=0．133kPa），总有效率为82．52％。氯沙坦钾片组降压幅度为（19±12）／（15±7）mmHg，总有效率为83．15％。两药均有良好的降压作用及相近的降压疗效（治疗前后组内P〈0．05），组间差异无统计学意义（均P〉0．05）。依普沙坦的服药顺从性为100％。两组治疗前后血钾、钠、氯、尿素氮、肌酐、血尿酸、血糖、血脂、肝功能等生化指标差异无统计学意义（P〉0．05）。结论 依普沙坦是长效的降压制剂，服药顺从性好，不良反应少。     

氯沙坦对糖尿病大鼠腹主动脉超微结构的影响

目的 :探讨糖尿病大鼠腹主动脉超微结构改变及血管紧张素Ⅱ受体拮抗剂 (ATR)氯沙坦对其影响。方法 :将健康的Wistar大鼠 30只随机分为正常对照组 (NC)、糖尿病对照组 (DC)、糖尿病氯沙坦治疗组 (DL) ,每组各10只。用链脲佐菌素 6 0mg kg腹腔注射复制糖尿病模型 ,造模后第 2天起DL组每天给予氯沙坦 2 0mg kg ,每周监测血糖 ,4周末取腹主动脉作电镜观察。结果 :DC、DL组血糖明显升高 ,4周后电镜显示 ,DC组腹主动脉逐渐出现内皮细胞肿胀、内弹力层中断 ,并出现平滑肌细胞 (SMC)伸入内膜 ,而DL组病变明显减轻。结论 :4周糖尿病大鼠腹主动脉即出现超微结构改变 ,氯沙坦能改善这种病理变化 ,ATR对糖尿病大鼠腹主动脉可能有一定保护作用     

氯沙坦对高血压血浆神经肽Y含量的干预研究

目的 观察应用氯沙坦前后高血压患者血浆神经肽Y(NPY)含量的变化,探讨血管紧张素Ⅱ(AⅡ)受体拮抗剂与NPY的相关性。方法 采用放免法测定40例高血压患者应用氯沙坦前后血浆NPY的含量及AⅡ水平,同期测定另外40例高血压患者应用美托洛尔前后血浆NPY的含量及AⅡ水平。结果40例高血压患者应用氯沙坦前后血浆NPY水平分别为(152.4±12.3)pg/ml、(125.5±9.5)pg/ml,P<0.01;血浆AⅡ水平分别为(49.6±7.1)pg/ml、(62.4±7.8)pg/ml,P<0.01。40例高血压患者应用美托洛尔前后血浆NPY水平分别为(144.1±11.3)pg/ml、(140.6±12.2)pg/ml,P>0.05;血浆AⅡ水平分别为(45.5±5.8)pg/ml、(48.3±7.2)pg/ml,P>0.05。治疗后2组之间比较,NPY、AⅡ水平均有非常显著性差异(P<0.01)。结论 氯沙坦能影响血浆NPY水平,提示该药降压的过程中有NPY参与的因素,而美托洛尔却不影响血浆NPY水平。     

氯沙坦与依那普利对原发性高血压的临床疗效对比

目的　比较氯沙坦与依那普利治疗原发性高血压、逆转高血压左室肥厚及改善舒张功能的临床疗效。方法　将原发性高血压伴左室肥厚者 6 4例 ,随机分为氯沙坦组和依那普利组 ,分别给予氯沙坦 2 5～ 10 0mg d ,依那普利 10～ 2 0mg d ,若达不到有效水平 ,加用双氢克尿噻 12 .5～ 5 0mg d ,观察 3个月 ,超声心动图测量治疗前后左室肥厚及舒张功能指标。结果　氯沙坦与依那普利均能有效安全地降低血压 ,并能逆转高血压左室肥厚 ,改善左室舒张功能 ,且两组间差异无显著性 (P >0 .0 5 )。结论　氯沙坦与依那普利在降低血压、逆转高血压左室肥厚、改善左室舒张功能等方面疗效相近。     

氯沙坦合用小剂量双克对高血压合并高尿酸血症患者尿酸的影响

目的 :探讨氯沙坦合用小剂量双克对高血压合并高尿酸血症病人的降尿酸作用。方法 :4 6例高血压合并高尿酸血症患者 ,随机分为氯沙坦组 (n =19)、氯沙坦 +双克组 (n =15 )、对照组 (n =12 ) ,分别予氯沙坦 5 0mgqd、氯沙坦 5 0mg +双克 12 .5mgqd ,洛汀新 10mgqd、观察两周 ,其间三组均不使用其他影响尿酸的药物 ,并观察血尿酸变化。结果 :氯沙坦和氯沙坦 +双克组均有明显降低血清尿酸水平作用 (p <0 .0 0 1) ,两组间降血尿酸效果无明显差别 (p >0 .0 5 ) ,对照组治疗前后血清尿酸无明显差异。结论 :氯沙坦 +双克后仍有良好的降血尿酸作用     

Bradykinin-induced water intake and brain fos-like immunoreactivity in rats

We have previously shown that peripheral injection of bradykinin in combination with the kinase II inhibitor, captopril, to rats produces a robust water intake. We now extend this observation to another kinase II inhibitor, enalapril. Water intake increases with dose of dose of bradykinin, but has an inverted U-shaped relationship with dose of kininase II inhibitor. The induced water intake is completely blocked by peripheral administration of the bradykinin antagonist, Hoe 140, and is partly attenuated by peripheral injection of an angiotensin (Ang) II receptor antagonist, losartan. Relative to captopril alone, the combination of captopril and bradykinin greatly elevated plasma renin activity, but did not reduce blood pressure. We further show that, while either bradykinin or enalapril alone induce little or no Fos-like immunoreactivity in areas of the brain related to fluid balance, their combination induces staining in many cells in the supraoptic and paraventricular magnocellular nuclei, as well as along the lamina terminalis. These data suggest that bradykinin may have a role in regulation of fluid balance, partly mediated through Ang II.     

Antagonist effect of losartan on angiotensin II induced contraction in five isolated smooth muscle assays

Antagonist effect of losartan, a nonpeptide antagonist of angiotensin II, on angiotensin II induced contractile response was studied in five isolated smooth muscle assays. In the rabbit aorta and guinea-pig stomach assays, losartan competed with angiotensin II for the angiotensin receptors in an apparently simple manner, that is compliance with the basic criteria of Schild analysis for simple competition. Noncompliance, however, was observed in the guinea-pig ileum, rat ileum and guinea-pig trachea assays where losartan induced nonparallel rightward shifts of angiotensin II E/log[A] curved and the Schild plots were found to have slopes greater than unity. The observed deviations from simple competitive antagonism appeared to be different from those reported earlier, and a possible explanation involving tissue-dependent noncompetitive factor(s) is discussed.