缬沙坦对慢性心力衰竭患者血浆脑钠素水平及左室收缩功能疗效的研究

目的 探讨慢性心力衰竭(CHF)患者在常规治疗基础上加用缬沙坦治疗12周后脑钠素(BNP)水平的变化及心功能的疗效.方法 应用化学发光法测定52例CHF患者治疗前、后和18例对照组血浆BNP浓度:用多普勒超声心动图测定CHF组左室舒张末期内径(LVEDD)及左室射血分数(LVEF).结果 CHF患者血浆BNP水平(456±253)Pg/mL较对照组(28±6)pg/mL明显增高(P＜0.01);不同心功能患者血浆BNP水平差异亦有显著意义,依次为Ⅳ级＞Ⅲ级＞Ⅱ级(P＜0.01),CHF组BNP水平升高与心力衰竭程度呈正相关(r=0.672,P＜0.01).缬沙坦治疗后血浆BNP水平明显下降,与治疗前比较差异有非常显著性(P＜0.01).LVEF有所提高,LVEDD明显缩小与治疗前比较均差异有显著性(P＜0.05).结论 血浆BNP水平可以反映心力衰竭严重程度、作为治疗心力衰竭的一个可靠观察指标.缬沙坦能显著降低脑钠素水平,改善心功能.在心力衰竭的治疗中起着重要作用.     

坎地沙坦在胺碘酮治疗持续性心房颤动中的作用

目的观察血管紧张素Ⅱ受体拮抗剂坎地沙坦联合胺碘酮治疗对持续性心房颤动（简称房颤）复律和维持窦性心律的影响。方法 68例持续性房颤患者随机分为A组34例,B组34例。A组单独给予胺碘酮治疗,B组联合给予胺碘酮和坎地沙坦治疗。结果 B组转复房颤为窦性心律的成功率明显高于A组（73.52%vs52.94%,P〈0.01）,至6个月时仍维持窦性心律的比例亦高于B组（88.00%vs66.67%,P〈0.05）。结论联合胺碘酮和坎地沙坦转复房颤并维持窦性心律的比例高于单独使用胺碘酮。     

迪之雅对糖尿病肾病治疗效果的临床研究

目的：探讨迪之雅对糖尿病肾病治疗效果。方法：将100例糖尿病肾病患者,分为糖尿病肾病组1和糖尿病肾病组2,再随机分为迪之雅组和对照组。结果：治疗16周,迪之雅组24h尿蛋白测定、尿β2微球蛋白水平均有明显下降,血清一氧化氮上升,血浆内皮素1水平明显下降。结论：提示迪之雅对糖尿病肾病的治疗能取得较好的效果,从远景上可延缓糖尿病肾病患者的肾功能损害。     

国产坎地沙坦酯治疗轻中度原发性高血压的随机双盲临床试验

目的:评价国产坎地沙坦酯治疗轻、中度高血压的疗效和安全性。方法:采用随机对照双盲临床试验设计,对58例高血压病患者随机分为试验组给予坎地沙坦酯片(=29,8mg/d)或对照组给予厄贝沙坦片(=29,150mg/d);2w后血压未正常者加药1片,疗程4w。结果:试验组和对照组的治疗2w时降压有效率分别为75.86%和37.93%,两组间比较差异有显著性(P<0.05);4w后试验组和对照组的降压有效率分别为89.66%和79.33%,两组比较无差异。治疗4w后试验组坐位、立位收缩压的降压幅度分别为27.52±11.90mmHg、24.59±11.87mmHg与对照组20.72±9.27mmHg、15.90±16.22mmHg相比有差异,P<0.01;P<0.05。两组不良反应发生率相似。结论:国产坎地沙坦酯与厄贝沙坦均有明显的降压效果,不良反应发生少,耐受性好。国产坎地沙坦酯对收缩压控制较好。     

坎地沙坦阻断血管紧张素Ⅱ介导的原代急性髓样白血病细胞增殖的作用及机制

目的: 观察血管紧张素Ⅱ 1型受体(AT1R)拮抗剂坎地沙坦抑制血管紧张素Ⅱ(Ang Ⅱ)介导的原代急性髓样白血病(AML)细胞增殖的作用及机制。方法: MTT法观察Ang Ⅱ对原代AML细胞、正常骨髓单个核细胞增殖的影响以及坎地沙坦和AT2R拮抗剂 PD123319对AngII促原代AML细胞增殖的拮抗作用; Western blotting法观察坎地沙坦和PI3K抑制剂对原代AML细胞Akt磷酸化的影响。结果: AngII能剂量和时间依赖性促进原代AML细胞增殖(P<0.05),而对正常骨髓无此作用。坎地沙坦随浓度和时间依赖性阻断Ang II作用下白血病细胞增殖(P<0.05)。PI3K抑制剂可抑制Ang II促进原代AML细胞的增殖(P<0.05),坎地沙坦能明显下调Ang II增加原代AML细胞Akt的磷酸化水平(P<0.05)。结论: 坎地沙坦通过抑制PI3K/Akt信号转导途径抑制Ang II/AT1R介导的白血病细胞增殖。     

Brain renin-angiotensin--a new look at an old system

The classic renin-angiotensin system (RAS) is described as a circulating hormone system focused on cardiovascular and body water regulation, with angiotensin II as its major effector. Detlef Ganten's discovery some years ago of an independent local brain RAS composed of the necessary functional components (angiotensinogen, peptidases, angiotensins and specific receptor proteins) significantly expanded the possible physiological and pharmacological functions of this system. This review first describes the enzymatic pathways resulting in active angiotensin ligands and their interaction with AT(1), AT(2) and AT(4) receptor proteins. We discuss the characterization and distribution of the AT(1) and AT(2) receptor subtypes and the current controversy over the identity of the AT(4) receptor subtype. Research findings favoring the candidates insulin-regulated aminopeptidase (IRAP) and the type 1 tyrosine kinase receptor c-Met, are presented. Next, we summarize current research efforts directed at the use of angiotensin analogues in the treatment of clinical disorders such as memory dysfunction, cerebral blood flow and cerebroprotection, stress, depression, alcohol consumption, seizure, Alzheimer's and Parkinson's diseases, and diabetes. The use of ACE inhibitors, and AT(1) and/or AT(2) receptor blockers, has shown promise in the treatment of several of these pathologies. The development of blood-brain barrier penetrant AT(4) receptor agonists and antagonists is of major importance regarding the continuing evaluation of the efficacy of new treatment approaches.     

A chitosan-graft-PEI-candesartan conjugate for targeted co-delivery of drug and gene in anti-angiogenesis cancer therapy

A multifunctional copolymer–anticancer conjugate chitosan-graft-polyethyleneimine-candesartan (CPC) containing low molecular weight chitosan (CS) backbone and polyethyleneimine (PEI) arms with candesartan (CD) conjugated via an amide bond was fabricated as a targeted co-delivery nanovector of drug and gene for potential cancer therapy. Here, CD was utilized to specifically bind to overexpressed angiotensin II type 1 receptor (AT₁R) of tumor cells, strengthen endosomal buffering capacity of CPC and suppress tumor angiogenesis. The self-assembled CPC/pDNA complexes exhibited desirable and homogenous particle size, moderate positive charges, superior stability, and efficient release of drug and gene in vitro. Flow cytometry and confocal laser scanning microscopy analyses confirmed that CD-targeted function and CD-enhanced buffering capacity induced high transfection, specific cellular uptake and efficient intracellular delivery of CPC/pDNA complexes in AT₁R-overexpressed PANC-1 cells. In addition, CPC/wt-p53 complexes co-delivering CD and wild type p53 (wt-p53) gene achieved synergistic angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor (VEGF) mRNA and protein via different pathways in vitro, as compared to mono-delivery and mixed-delivery systems. In vivo investigation on nude mice bearing PANC-1 tumor xenografts revealed that CPC/wt-p53 complexes possessed high tumor-targeting capacity and strong anti-tumor activity. Additional analysis of microvessel density (MVD) demonstrated that CPC/wt-p53 complexes significantly inhibited tumor-associated angiogenesis. These findings suggested that CPC could be an ideal tumor-targeting nanovector for simultaneous transfer of drug and gene, and a multifunctional CPC/wt-p53 co-delivery system with tumor-specific targetability, enhanced endosomal buffering capacity and synergistic anti-angiogenesis efficacy might be a new promising strategy for effective tumor therapy.     

Blockade of renin-angiotensin system ameliorates renal injury in NIDDM model rats

Background. Recently, inhibition of the renin-angiotensin system has been reported to be effective for patients with diabetic nephropathy. In this study, we examined the renal protective effects of candesartan cilexetil (TCV-116) in Wistar fatty rats, a model of non-insulin-dependent diabetes mellitus (NIDDM) with renal injuries. Methods. Twelve-week-old Wistar fatty rats received candesartan cilexetil (0.3 or 1 mg/kg) or enalapril (10 mg/kg) daily, administered orally, for 16 weeks. Routine laboratory parameters, such as urinary albumin and total protein excretion, were measured every 4 weeks, and renal function tests and histopathological studies were carried out at the end of the experiment. Results. In the 12-week-old Wistar fatty rats, plasma glucose and insulin levels were significantly higher than those in age-matched Wistar lean rats (normal controls). Urinary albumin and total protein excretion was slightly but significantly increased as compared to these parameters in Wistar lean rats, and increased further with time. Daily administration of candesartan cilexetil or enalapril inhibited the increase in urinary albumin and total protein excretion without affecting plasma glucose and insulin levels. In histopathological studies, candesartan cilexetil (0.3 and 1 mg/kg) and enalapril (10 mg/kg) prevented the glomerular injury observed in vehicle-treated rats. Candesartan cilexetil (1 mg/kg) and enalapril also inhibited tubular changes. Systolic blood pressure in the drug-treated groups was significantly decreased compared with that in vehicle-treated rats. Conclusions. Inhibitors of the renin-angiotensin system ameliorated proteinuria and the pathological changes of renal injuries in this NIDDM model. Candesartan cilexetil may be useful for the treatment of NIDDM patients with renal damage. Received: March 1, 1999 / Accepted: June 13, 2000     

坎地沙坦联合复方丹参滴丸对老年原发性高血压患者肾功能的影响

目的 探讨坎地沙坦联合复方丹参滴丸对老年原发性高血压患者肾功能的影响.方法 老年原发性高血压合并肾功能损害患者80例.随机分为对照组40例和治疗组40例,对照组口服坎地沙坦4 mg,1次/d;治疗组在对照组基础上加用复方丹参滴丸10粒,3次/d;随访6个月观察其血肌酐、尿素氮、内生肌酐清除率的变化.结果 (1)两组药物都能明显降低血压.治疗组血压下降的稳定性优于对照组,差异无统计学意义(P＞0.05).(2)治疗组治疗前血肌酐、尿素氮及内生肌酐清除率分别为(196.8±2.6)μmol/L、(9.84±3.20) mmol/L、(58.1±4.9)ml/min,治疗组随访6个月血肌酐、尿素氮及内生肌酐清除率分别为(104.6±6.5)μmol/L、(6.21±4.80) mmol/L、(117.2±6.4) ml/min,血肌酐、尿素氮明显降低,内生肌酐清除率明显升高,差异有统计学意义(t值分别为2.213、2.302、2.136,P均＜0.05),对照组随访6个月后血肌酐、尿素氮和内生肌酐清除率也有所降低但差异无统计学意义(P＞0.05).结论 两种药物联合应用可能有协同作用,能更好地遏制肾脏疾病的进展.     

The angiotensin II receptor antagonist candesartan cilexetil (TCV-116) ameliorates retinal disorders in rats

Aims/hypothesis. The results of the EUCLID trial (EURODIAB Controlled Trial of Lisinopril in Insulin-dependent Diabetes Mellitus) highlighted the importance of the renin-angiotensin system in the pathogenesis of diabetic retinopathy. Candesartan cilexetil (TCV-116), a potent angiotensin II (AII) receptor antagonist, has beneficial effects on hypertension as well as on heart, renal and cerebrovascular disease. We aimed to evaluate the effectiveness of candesarten cilexetil in ameliorating retinal disorders induced by hyperglycaemia. Methods. We compared retinal vascular endothelial growth factor (VEGF) mRNA expression and the latencies of retinal oscillatory potentials in TCV-116-treated and control groups of stroke-prone spontaneously hypertensive rats with streptozocin (STZ)-induced diabetes. Results. Retinal VEGF mRNA expression was significantly higher and the latencies of oscillatory potentials were significantly elongated in STZ-treated spontaneously hypertensive rats compared with a non-treated spontaneously hypertensive rat group matched for age. These changes were dependent on hyperglycaemia but independent of hypertension. Treatment with TCV-116 (3 mg/kg) significantly diminished retinal VEGF mRNA expression and the latencies of oscillatory potential peaks, but had no effect on plasma glucose concentrations. Conclusion/interpretation. These results suggest that TCV-116 is effective in preventing the development of diabetic retinopathy already in the early stages. [Diabetologia (2001) 44: 883–888] Received: 23 December 2000 and in revised form: 2 March 2001