血管紧张素Ⅱ在肝硬化肾钠潴留中的作用

目的 应用血管紧张素拮抗剂缬沙坦探讨血管紧张素Ⅱ在肝硬化肾钠潴留中的作用.方法 64例肝硬化患者随机分为观察组和对照组,分别给予口服缬沙坦(80 mg/d)一周和常规治疗.用药前后分别测定血浆肾素活性(plasma renin activity, PRA)、血浆血管紧张素Ⅱ(angiotensin Ⅱ, AⅡ)及24 h尿钠(urinary sodium excretion per 24 h, UNa ).结果 用药后PRA、AⅡ升高,同时UNa 排出增加,有腹水和肝损严重者尤为明显.结论 缬沙坦使尿钠排出增加,表明AⅡ在肝硬化肾钠异常代谢中起重要作用.     

缬沙坦对糖尿病大鼠肾脏内皮素受体基因表达的影响

目的观察血管紧张素受体拮抗剂（ARB）缬沙坦对糖尿病大鼠肾脏内皮素受体A（ETA）、内皮素受体B（ETB）基因表达的影响。方法SD大鼠，制备链脲佐菌素诱导的糖尿病（DM）模型，设正常对照组、糖尿病对照组、小剂量缬沙坦治疗组（10mg·kg^-1·d^-1）、大剂量缬沙坦治疗组（50mg·kg^-1·d^-1）、极大剂量治疗组（100mg·kg^-1·d^-1）。9周后采用逆转录-聚合酶链反应方法观察肾脏ETA、ETB基因表达情况。结果与正常对照组相比，糖尿病对照组大鼠肾ETA、ETB基因表达明显升高（P〈0．01）；与小剂量治疗组相比，大剂量治疗组上述指标明显改善（P〈0．01）；与大剂量治疗组相比，极大剂量治疗组上述指标无明显变化。结论缬沙坦通过降低肾内ETA、ETB表达而达到肾脏保护作用，而且此效应大剂量优于小剂量。     

缬沙坦、氨氯地平对老年高血压病患者血小板活化及纤溶活性的影响及比较

目的 :探讨缬沙坦、氨氯地平对老年高血压病(EH)患者血小板活化及纤溶活性的影响。方法 :采用双抗体夹心酶联免疫吸附法和发色底物法分别测定 30例正常老年人和 5 7例老年EH患者血浆中血小板α颗粒膜蛋白 (GMP 14 0 )和组织型纤溶酶原激活剂 (t PA)及其抑制物 (PAI 1)水平。 5 7例老年EH患者应用缬沙坦 (2 9例 )或氨氯地平 (2 8例 )治疗12wk。结果 :老年EH患者GMP 14 0含量、PAI 1活性明显升高 (P <0 .0 0 1或P <0 .0 1) ,t PA活性明显降低 (P <0 .0 1) ;GMP 14 0含量与PAI 1水平呈正相关 (P <0 .0 1)。治疗后 ,老年EH患者GMP 14 0含量及PAI 1活性均明显下降 (P <0 .0 1;P <0 .0 5 ) ,t PA活性显著升高 (P <0 .0 5 ) ,两用药组间差异无显著性 (P >0 .0 5 )。结论 :老年EH患者血小板功能及纤溶活性异常 ;缬沙坦、氨氯地平均能有效抑制血小板活化、改善纤溶活性     

缬沙坦长期治疗原发性高血压病人的安全性和疗效

目的 :评估缬沙坦长期治疗原发性高血压的安全性与疗效。方法 :门诊轻、中度高血压的病人3 2例 (男性 2 3例 ,女性 9例 ,年龄 5 1a±s 9a) ,服用缬沙坦 80mg·d-1,wk 4后血压控制不满意者加量至 1 60mg·d-1,共治疗 2 4wk。结果 :舒张压下降程度在治疗后wk 4,8,1 6,2 4末分别为 :1 .6kPa±0 .9kPa,2 .0kPa± 0 .8kPa,2 .1kPa± 1 .0kPa,1 .8kPa± 0 .8kPa,较治疗前差异均有非常显著意义 (P<0 .0 1 )。wk 4,2 4治疗有效率分别为 78%与 75% (P >0 .0 5 )。未见干咳发生 ,不良反应少 ,耐受性良好。结论 :缬沙坦长期治疗轻、中度原发性高血压安全有效     

Stabilization and regression of albuminuria in Chinese patients with type 2 diabetes: A one-year randomized study of valsartan versus enalapril

This study was designed to compare the short-term (1-y) tolerability and antiproteinuric efficacy of enalapril and valsartan in patients with type 2 diabetes. Fortytwo patients with normal renal function or early-stage nephropathy were recruited in Hong Kong and randomized to valsartan 80 mg/day or enalapril 5 mg/day; the doses were increased to 160 mg and 10 mg daily, respectively, as tolerated. Early-morning urine was analyzed for albumin and creatinine and 24-hour urinary albumin excretion at baseline and 1 year after therapy began. Twenty-two patients were randomized to valsartan and 20 to enalapril. The 2 treatment groups were similar in terms of age, sex distribution, and duration of diabetes or hypertension. Blood pressure decreased to a similar extent (−2.5% to −5.0%) with each drug. Similarly, the 24-hour urinary albumin excretion decreased by 5% to 6% with each drug. The albumin-creatinine ratio in early-morning urine samples and plasma creatinine levels decreased in the valsartan group and increased in the enalapril group, but the difference was not significant. Plasma potassium levels were stable in both groups at the end of study. Cough was reported by 7 (35%) patients receiving enalapril and none of those receiving valsartan (P=.003). In conclusion, enalapril and valsartan both reduced blood pressure and albuminuria to a similar extent with 1 year of therapy in Chinese patients with type 2 diabetes and normal renal function or early-stage nephropathy. Fewer adverse events were reported with valsartan, but both drugs appear to be relatively safe.     

卡维地洛联合缬沙坦治疗心力衰竭并心房颤动的效果

目的:评估联合应用卡维地洛与缬沙坦治疗心力衰竭并心房颤动的疗效和安全性。方法:46例心力衰竭并心房颤动患者随机分为两组,应用缬沙坦80 mg/d,1周后,对照组维持原治疗,治疗组缬沙坦联用卡维地洛(5~20mg/d)治疗4个月。治疗前后分别行超声心动图和动态心电图检查,评价左室功能和心室率。结果:治疗前后治疗组的静息心室率分别为(97.8±7.0)次/min和(75.4±6.0)次/min,治疗前后比较差异有统计学意义(t=15.67,P<0.01),其心室率变化较对照组明显(t=5.48,P<0.01)。治疗组的左室射血分数、左室短轴缩短率、心排血量和E/A比值有明显改善,两组比较差异有统计学意义(t=3.45~36.89,P<0.01)。两组患者治疗前后均未发现明显不良反应。结论:卡维地洛与缬沙坦合用治疗心力衰竭并心房颤动安全有效。     

Effect of valsartan on erythropoietin and hemoglobin levels in stage III-IV chronic kidney disease patients

Angiotensin-converting enzyme inhibitors (ACEIs) were accepted as a potential cause of inadequate epoetin response in chronic kidney disease (CKD) patients. We aimed to determine the effects of valsartan, an angiotensin receptor blocker (ARB), on serum ertyhropoietin levels and on certain biochemical and haematological parameters in hypertensive CKD patients. Twenty-two stage III-IV CKD patients (mean age; 56.8 +/- 8.9 years, 12 male 10 female) were included in the study. Before initiating the treatment, current anti-hypertensive treatments (if any) were discontinued, and blood samples were collected after a washout period of 3 weeks. Valsartan 80 mg/day was started, and additional anti-hypertensive agents were given according to study protocol if needed. One way Anova and paired t-tests were used for statistical comparisons. Serum blood urea nitrogen (BUN), creatinine, uric acid, potassium, haemoglobin and erythropoietin values were measured, and glomerular filtration rates were calculated before and 3, 6 and 90 days after valsartan treatment, a significant reduction in EPO level was observed at 3rd (19.6 +/- 24.0 vs. 13.8 +/- 8.5, p = 0.010), 6th (12.1 +/- 7.6, p = 0.009), and 90th days (8.3 +/- 5.4, p = 0.007). When pre-treatment values were compared with 90th day results, no significant change was observed in terms of hgb, htc, serum BUN, creatinine, uric acid, potassium, and GFR values. In conclusion, valsartan, an ARB, did not decrease haemoglobin levels in stage III-IV CKD patients despite significant reduction in serum erythropoietinlevels, so ARBs may be preferred to ACEIs in CKD patients when indicated.     

Valsartan and coronary haemodynamics in early post-myocardial infarction in rats

Angiotensin II AT1 receptor blockade (AT1-) has been shown to prolong survival in post-myocardial infarction (MI) heart failure in rats. In this study, we investigated whether an early AT1-induced improvement in coronary vasodilatation reserve (CVR) might be involved in this beneficial effect. Wistar rats with MI were treated daily and orally for 6 weeks with valsartan, 5 (MI-V5) or 50 mg/kg (MI-V50). MI-controls and sham-operated rats (S-controls) received no treatment. Subsequently, systemic and coronary haemodynamics (at baseline and at maximal vasodilatation, CVR fluospheres) were investigated in the conscious state, and cardiac remodelling (hypertrophy and fibrosis) was assessed. As compared to MI-controls. valsartan (5 mg/kg), had no effect on systemic haemodynamics or myocardial hypertrophy and fibrosis development, gave slightly improved basal left and right ventricular coronary flow and resistance values, but decreased left and right CVR values. Valsartan (50 mg/kg), decreased blood pressure (-11%) and left ventricular end diastolic pressure (-32%), limited the development of cardiac hypertrophy (19%) but not that of fibrosis, slightly improved basal left ventricular flow and resistance values but only the right ventricular CVR value was increased. We conclude that in rats with post-MI. an early AT1-induced improvement in coronary haemodynamics is not responsible for the long-term survival prolongation observed. Furthermore. that cardiac hypertrophy was prevented whereas fibrosis was not, suggests that the latter is a pivotal determinant of CVR.     

The benefits of valsartan in the treatment of heart failure: results from Val-HeFT

Angiotensin II receptor blockers (ARBs) are the most recent class of anti-hypertensive drug to enter clinical use for chronic heart failure (CHF). In the landmark Valsartan Heart Failure Trial (Val-HeFT), valsartan reduced the risk of the combined endpoint of all-cause mortality and morbidity by 13.2% over a 2-year follow-up. Although it significantly improved a pre-specified primary endpoint, it did not improve the endpoint of all-cause mortality. Valsartan administered to patients not receiving angiotensin-converting enzyme inhibitors (ACEI) at baseline reduced the endpoint of all-cause mortality by 33% and the combined endpoint of mortality and morbidity by 44%, compared with placebo. Based on these findings, valsartan became the first ARB to be approved by the US Food and Drug Administration for the treatment of New York Heart Association class II-IV HF in patients who are intolerant of ACEIs. This review provides a summary of the key Val-HeFT results and their implications in the treatment of CHF patients.     

Systolic Blood Pressure in Heart Failure With Preserved Ejection Fraction Treated With Sacubitril/Valsartan

BackgroundGuidelines recommend targeting systolic blood pressure (SBP) <130 mm Hg in heart failure with preserved ejection fraction (HFpEF) with limited data.ObjectivesThis study sought to determine the optimal achieved SBP and whether the treatment effects of sacubitril/valsartan on outcomes are related to BP lowering, particularly among women who derive greater benefit from sacubitril/valsartan.MethodsUsing 4,795 trial participants, this study related baseline and time-updated mean achieved SBP quartiles (<120, 120 to 129, 130 to 139, ≥140 mm Hg) to the primary outcome (cardiovascular death and total heart failure hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 16-week visit, the study assessed the relationship between SBP change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and N-terminal pro−B-type natriuretic peptide (NT-proBNP). The study analyzed whether the BP-lowering effects of sacubitril/valsartan accounted for its treatment effects.ResultsAverage age was 73 ± 8 years, and 52% of participants were women. After multivariable adjustment, baseline and mean achieved SBP of 120 to 129 mm Hg demonstrated the lowest risk for all outcomes. Sacubitril/valsartan reduced SBP by 5.2 mm Hg (95% confidence interval: 4.4 to 6.0) compared with valsartan at 4 weeks, which was not modified by baseline SBP. However, sacubitril/valsartan reduced SBP more in women (6.3 mm Hg) than men (4.0 mm Hg) (interaction p = 0.005). Change in SBP was directly associated with change in NT-proBNP (p < 0.001) but not KCCQ-OSS (p = 0.40). The association between sacubitril/valsartan and the primary outcome was not modified by baseline SBP (interaction p = 0.50) and was similar when adjusting for time-updated SBP, regardless of sex.ConclusionsBaseline and mean achieved SBP of 120 to 129 mm Hg identified the lowest risk patients with HFpEF. Baseline SBP did not modify the treatment effect of sacubitril/valsartan, and the BP-lowering effects of sacubitril/valsartan did not account for its effects on outcomes, regardless of sex. (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)