氯沙坦和哌唑嗪调节早期高血压大鼠体内降钙素基因相关肽反应的差异

目的：探讨高血压早期大鼠体内降钙素基因相关肽（CGRP）的变化,并观测两类降压药物,氯沙坦或哌唑嗪在降压过程中对CGRP的反应差异。方法：采用经典的两肾一夹型高血压大鼠（Goldblatt,2K1C）为研究模型,夹尾法测定大鼠清醒状态下血压,通过公式计算出平均动脉压;放射免疫法血浆内CGRP和血管紧张素Ⅱ（AngⅡ）的含量。反转录聚合连反应（RT-PCR）测定脊髓背根神经节中CGRP mRNA的表达。结果：收缩压、平均动脉压在结扎肾动脉10d后较对照组快速升高（P〈0．01）,给予氯沙坦或哌唑嗪治疗5d后,血压明显降低（P〈0．01）;实验末,高血压未治疗组血浆中AngⅡ、CGRP浓度（P〈0．01,P〈O．01）和脊髓背根神经节中的CGRP mRNA的表达明显升高（P〈0．05）,高血压氯沙坦治疗组可进一步升高大鼠血浆中AngⅡ、CGRP浓度（P〈0．01,P〈0．01）和脊髓背根神经节中的CGRP mRNA的表达（P〈0．05）;但在高血压哌唑嗪治疗组大鼠血浆中AngⅡ变化不显著（P〉0．05）,但CGRP浓度和脊髓背根神经节中的CGRP mRNA的表达与未治疗组相比显著降低（P〈0．05,P〈0．01）。结论：在肾血管性高血压早期含CGRP感觉神经功能存在代偿性增高,氯沙坦或哌唑嗪的不同降压机制也可能与其影响体内CGRP合成和释放差异有关。     

丹参多酚酸盐在糖尿病肾病治疗中的临床研究

目的:观察丹参多酚酸盐改善糖尿病肾病(DN)患者抗氧化及肾功能的临床效果。方法:将90例DN患者随机分为治疗组和对照组,每组45例,2组均给予降糖降压等基础治疗,对照组口服氯沙坦钾片治疗,50mg,qd;治疗组给予静脉注射丹参多酚酸盐,200mg,qd,2组均治疗2周。检测并比较2组治疗前后血糖、肾功能及氧化应激指标水平,观察治疗期间药物不良反应发生情况。结果:治疗后对照组有效率为73.33%(33/45),治疗组为91.11%(41/45),2组间治疗有效率差异有统计学意义(P<0.05)。治疗后2组血肌酐(Scr)、24h尿蛋白(24h Upro)、尿素氮(BUN)、胱抑素C(CysC)、尿蛋白排泄率(UAER)、β2微球蛋白(β2-MG)等肾功能指标与治疗前比较均降低(P<0.05),且治疗组上述各项肾功能指标改善程度明显优于对照组(P<0.05)。治疗后2组血清活性氧(ROS)、丙二醛(MDA)与治疗前比较均降低,超氧化物歧化酶(SOD)均升高(P<0.05),且治疗组上述各项氧化应激指标改善程度均显著高于对照组(P<0.05),2组治疗前后血糖水平无明显变化(P>0.05)。2组不良反应发生率比较无明显差异(P>0.05)。结论:丹参多酚酸盐可显著改善DN患者氧化应激及肾功能指标,疗效确切,安全性高。     

氯沙坦对90%门静脉结扎大鼠血清肝细胞生长因子水平及肝再生的影响

目的探讨氯沙坦对90%门静脉分支结扎(portal branch ligation,PBL)大鼠血清肝细胞生长因子(hepatocyte growth factor,HGF)水平及肝再生的影响。方法 96只雄性Sprague-Dawley(SD)大鼠采用随机数字法分成2组:A组:单纯PBL组(对照组,n=48),B组:PBL+2 mg/(kg.d)氯沙坦干预组(治疗组,n=48),分别于术后0、6、12、24、48、72、120、168 h取大鼠肝脏称质量并计算未结扎侧肝质量占总肝质量比例,心脏取血测ALT及AST,酶联免疫吸附实验(ELISA)检测血清HGF水平,免疫组化方法检测未结扎侧肝组织增殖细胞核抗原(PCNA)的表达。结果①治疗组未结扎侧肝质量与总肝质量比值在24~168 h明显高于对照组(P<0.01)。②PBL术后2组ALT值迅速升高,12 h达到高峰后逐渐降低。治疗组ALT值在12~48 h明显低于对照组(P<0.01);同时PBL术后两组ALT值后迅速升高,12 h达到高峰后逐渐降低。治疗组ALT值在12~72 h明显低于对照组(P<0.01)。③术后2组血清大鼠HGF浓度迅速升高,并在6 ...     

A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients : A placebo-controlled, forced titration study

The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a long-lasting binding to the human AT₁-receptor, to that of losartan on ambulatory BP (ABP) not only during the 24-h dosing interval but also during the day of a missed dose intake. After a 4-week placebo lead-in period, 268 patients with sitting diastolic BP 95 to 110 mm Hg and mean awake ambulatory DBP ≥85 mm Hg were randomized to receive either 8 mg of candesartan, 50 mg of losartan, or placebo for a 4-week period. Thereafter, the doses were doubled in all patients for an additional 4-week period. Ambulatory BP monitoring was performed for 36 h after dosing and clinic BP measured 48 h after dosing.

Candesartan cilexetil (16 mg) reduced ABP to a significantly greater extent than 100 mg of losartan, particularly for systolic ABP during daytime (P < .05), nighttime (P < .05), and 24-h (P < .01) periods, systolic (P < .01) and diastolic (P < .05) ABP between 0 and 36 h, and both systolic (P < .001) and diastolic (P < 0.001) ABP during the day of a missed dose. Clinic BP at 48 h after dosing was significantly reduced exclusively with 16 mg of candesartan. The differences in BP reduction between 8 mg of candesartan and 50 mg of losartan were statistically significant for systolic ABP during daytime (P < .01), nighttime (P < .05), 24-h (P < .01), 0 to 36 h (P < .05) and during the day of missed dose (P < .05). Moreover, although losartan did not significantly reduce ambulatory BP in a dose-related manner, ambulatory systolic and diastolic BP reductions with 16 mg of candesartan were significantly greater (P < .01 and < .001) than those seen with 8 mg of candesartan during every period at the ABP supporting a dose–response relationship.

In conclusion, this forced titration study in ambulatory hypertensive patients demonstrates that candesartan cilexetil provides significant dose-dependent reduction in both clinic and ambulatory BP in doses ranging from 8 to 16 mg once daily. Furthermore, candesartan cilexetil is superior to losartan in reducing systolic ABP and in controlling both systolic and diastolic ABP on the day of a missed dose. The differences observed between both agents are most likely attributable to a tighter binding to, and a slower dissociation from, the receptor binding site with candesartan cilexetil.     

氯沙坦对实验性糖尿病大鼠肾脏功能的保护作用

目的 :探讨氯沙坦对糖尿病肾病肾脏功能的保护作用。方法 :制作糖尿病大鼠模型 ,分成 3组 ,每组 15只 ,糖尿病治疗组给予氯沙坦灌胃 ,糖尿病组和正常对照组均给予等量生理盐水灌胃。分别于实验的wk 1,2 ,4取材 ,测定血糖、血肌酐、尿清蛋白、尿肌酐、尿α1 微球蛋白排泄率和血浆内皮素(ET)水平。结果 :糖尿病组大鼠出现血糖升高、肌酐清除率下降、尿清蛋白和尿α1 微球蛋白排泄率升高 ,与正常对照组相比差异有非常显著和显著意义(P <0 .0 1或P <0 .0 5 ) ,血浆ET水平升高 ,wk 2时与正常对照组间差异有非常显著意义 ;肌酐清除率、尿清蛋白和尿α1 微球蛋白排泄率等指标 ,治疗组与糖尿病组比较差异均有显著或非常显著意义。结论 :动物实验证实氯沙坦可减轻糖尿病肾病的肾功能损害 ,改善肾功能 ,具有肾脏保护作用     

洛沙坦和培哚普利对急性心肌梗死后左心室重塑的疗效比较

目的：观察洛沙坦和培哚普利对急性心肌梗死（AMI）患者，左心室重塑（LVRM）的治疗效应并进行比较。方法：AMI患者65例，随机分为3组。洛沙坦组22例，培哚普利组22例，对照组21例。对照组仅给予硝酸酯类、肠溶阿司匹林、肝素等常规治疗；洛沙坦组在常规治疗基础上加用洛沙坦25mg口服，每日1次；培哚普利组在常规治疗基础上加用培哚普利4mg口服，每日1次。分别在入院后第1天、14天、6个月时采用超声心动图，测定左心室舒张末期内径（LVDd）、左心室收缩末期内径（LVDs）、左心室射血分数（LVEF）并进行比较。结果：对照组14天及6个月时LVDd、LVDs较基础值增加，有显著性差异（P＜0．05）；洛沙坦组与培哚普利组14天及6个月时LVDd、LVDs与基础值比较轻度增加，与对照组比较明显缩小，有显著性差异（P＜0．05）；洛沙坦组与培哚普利组LVDd、LVDs变化无显著性差异（P＞0．05）。培哚普利组咳嗽发生率18％，洛沙坦组无1例发生副反应。结论：洛沙坦与培哚普利具有相似的抗左心室重塑的治疗效应，洛沙坦耐受性更好。     

Effects of Losartan-based therapy on the incidence of end-stage renal disease and associated costs in type 2 diabetes mellitus: A retrospective cost-effectiveness analysis in the United Kingdom

Background:

In the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, the primary composite end point was the 2-fold increase in baseline serum creatinine concentration, the development of end-stage renal disease (ESRD), or death. The effects of losartan used for the prevention or delay of progression of diabetic nephropathy to ESRD were compared with those of conventional anti-hypertensive treatment (control) (calcium channel blockers, diuretics, α-blockers, β-blockers, and centrally acting agents), but not angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists (AIIAs), in 1513 adults with type 2 diabetes mellitus (DM-2) and nephropathy. Both treatment groups received conventional antihypertensive therapy (calcium channel blockers, diuretics, α-blockers, β-blockers, and/or centrally acting agents). ACE inhibitors and AIIAs were not allowed during the study period. The relative risk (RR) for composite outcome was 25% less, and the RR for ESRD was 28% less, in the losartantreated group compared with the control group.

Objective:

The aim of this retrospective cost-effectiveness analysis was to use data from the RENAAL study to determine the survival benefits and lifetime direct medical costs of a losartan-based regimen for the prevention of ESRD in patients with DM-2 and nephropathy in the setting of the UK National Health Service (NHS).

Methods:

This analysis used life-years saved as the effectiveness measure. The effect of losartan-based treatment on ESRD risk was confined to the trial period (3.5 years). However, survival and the lifetime direct medical costs of managing ESRD were projected beyond the trial period to incorporate the full effects of ESRD on survival and resource use. The effect of altering key variables was examined using 1-way sensitivity analyses.

Results:

ESRD-related costs were significantly lower in patients receiving losartan-based treatment compared with those in the control group (savings per patient, 7390 [95% CI, 11,366-3414; P< 0.001] [1 = US −$1.75]). Incorporation of the cost of losartan into the assessment found reduced net costs (savings per patient, 6622 [95% CI, 10,591-2653; P= 0.001]). The projected mean number of life years saved due to ESRD risk reduction with losartan was 0.44 years (95% CI, 0.16-0.71; P = 0.002). Losartan treatment was found to save costs in all cases, even if the cost of renal replacement therapy for patients with ESRD was reduced by 50%.

Conclusion:

In this retrospective cost-effectiveness analysis using data from the RENAAL study, losartan-based treatment for the prevention or delay of progression of diabetic nephropathy to ESRD in patients with DM-2 and nephropathy was found to be potentially cost saving compared with conventional anti-hypertensive therapy from the perspective of the UK NHS.     

氯沙坦与吲哒帕胺单用和两药联合治疗老年高血压疗效比较

目的观察氯沙坦与吲哒帕胺单独应用或联合用药对原发性高血压患者血压、血钾、血糖、尿酸、血脂的影响。方法将符合诊断标准的150例老年高血压患者电脑随机分为3组，每组50例，进行用药前后自身对照试验，8周后检测各组血压、血钾、血糖、尿酸、血脂值。结果3组治疗后收缩压和舒张压均较前明显降低，联合治疗组降压幅度最大，氯沙坦组和联合治疗组治疗后尿酸值较治疗前降低，吲哒帕胺组治疗后血钾值较治疗前降低。结论氯沙坦与吲哒帕胺联合应用不仅具有协同降压作用，而且能降低尿酸，减轻吲哒帕胺引起的低钾血症。     

尼贝沙坦联合胺碘酮治疗阵发性心房颤动的临床观察

目的：观察尼贝沙坦联合胺碘酮治疗阵发性心房颤动的临床效果与安全性。方法：将60例阵发性心房颤动患者平分为治疗组与对照组各30例,在各种常规治疗的基础上,对照组加用尼贝沙坦治疗,治疗组加用贝沙坦联合胺碘酮治疗。结果：经过治疗后,两组都无死亡患者,治疗组总有效率为90.0%,对照组总有效率为70.0%,治疗组的临床疗效明显好于对照组（P〈O.05）。而对照组的脑栓塞和脑出血发生率都明显高于治疗组（P〈0.05）。结论：尼贝沙坦联合胺碘酮治疗阵发性心房颤动的临床效果好,安全性好,值得推广应用。