Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, Würzburg, Germany.
Kidney Blood Press Res. 2011;34(3):167-72. doi: 10.1159/000326805. Epub 2011 Apr 7.
Angiotensin II (ANG II) and advanced glycation end products (AGEs) exert genotoxic effects in vitro which were prevented by the ANG II type 1 (AT1) receptor blocker, candesartan. In end-stage renal disease (ESRD) the incidence of genomic damage is increased. A stimulation of the renin-angiotensin system and accumulation of AGEs could be involved.
We tested whether oral co-administration of candesartan modulates enhanced DNA damage in ESRD patients. Fifteen maintenance hemodialysis (MHD) patients with mild hypertension were treated with candesartan for 4.5 months. Fourteen MHD patients served as conventionally treated uremic controls. DNA damage was measured as micronucleus frequency (MNF) in peripheral blood lymphocytes and evaluated three times before candesartan therapy and afterwards every 6 weeks.
Compared to 14 healthy controls, MNF at baseline was significantly elevated in MHD patients. While in the conventionally treated MHD patients the enhanced DNA damage persisted, the co-administration of candesartan ameliorated the genomic damage significantly and independently of blood pressure changes.
Blockade of AT1 receptors with candesartan can reduce DNA damage in MHD patients. Long-term studies in larger patient groups are needed to investigate whether the improved genomic damage lowers atherosclerotic complications and cancer development.
血管紧张素 II（ANG II）和晚期糖基化终产物（AGEs）在体外具有遗传毒性作用，血管紧张素 II 型 1（AT1）受体阻滞剂坎地沙坦可预防这种作用。在终末期肾病（ESRD）中，基因组损伤的发生率增加。肾素-血管紧张素系统的刺激和 AGEs 的积累可能与此有关。
我们测试了口服坎地沙坦是否能调节 ESRD 患者增强的 DNA 损伤。15 名患有轻度高血压的维持性血液透析（MHD）患者接受坎地沙坦治疗 4.5 个月。14 名 MHD 患者作为常规治疗的尿毒症对照。通过外周血淋巴细胞微核频率（MNF）测量 DNA 损伤，并在坎地沙坦治疗前三次和之后每 6 周评估一次。
与 14 名健康对照者相比，MHD 患者的基线 MNF 显著升高。虽然在常规治疗的 MHD 患者中，增强的 DNA 损伤持续存在，但坎地沙坦的联合治疗显著改善了基因组损伤，且与血压变化无关。
用坎地沙坦阻断 AT1 受体可减少 MHD 患者的 DNA 损伤。需要进行更大患者群体的长期研究，以调查改善的基因组损伤是否降低动脉粥样硬化并发症和癌症的发生。
