Department of Experimental Hypertension, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Physiol Res. 2010;59(3):339-345. doi: 10.33549/physiolres.931900.
The relationship between angiotensin II (ANG II) and endothelin-1 (ET-1) is known to be complex; both peptides can initiate and potentiate the gene expression of each other. This pilot study investigated the effects of the AT(1) receptor blocker losartan or the direct renin inhibitor aliskiren on mean arterial pressure (MAP) and albuminuria and the renal ANG II and ET-1 levels. 3-month-old male Ren-2 transgenic rats (TGR) were treated either with losartan (5 mg kg(-1) day(-1)) or aliskiren (10 mg kg(-1) day(-1)) for 10 weeks. At the end of the experiment, rats were decapitated and cortical and papillary parts of kidneys were separated. Plasma and tissue ANG II levels were measured by RIA and tissue ET-1 concentrations by ELISA. In all four groups of animals ET-1 levels were lowest in renal cortex and more than 100-fold higher in the papilla. Cortical and papillary ET-1 concentrations in untreated TGR significantly exceeded those of control HanSD rats and were significantly depressed by both drugs. In both strains, papillary ANG II concentrations were moderately but significantly higher than cortical ANG II, TGR exhibited higher ANG II levels both in cortex and papilla as compared to control HanSD rats. Aliskiren and losartan at the doses used depressed similarly the levels of ANG II in cortex and papilla and reduced ET-1 significantly in the renal cortex and papilla below control levels in HanSD rats. Albuminuria, which was more than twice as high in TGR as in HanSD rats, was normalized with aliskiren and reduced by 28% with losartan, although MAP was reduced to a similar degree by both drugs. Despite similar reductions of MAP and renal ET-1 and ANG II levels aliskiren appears to be more effective than losartan, at the doses used, in reducing albuminuria in heterozygous hypertensive Ren-2 rats.
血管紧张素 II (ANG II) 和内皮素-1 (ET-1) 之间的关系是复杂的；这两种肽都可以启动和增强彼此的基因表达。这项初步研究调查了 AT(1)受体阻滞剂氯沙坦或直接肾素抑制剂阿利克仑对平均动脉压 (MAP) 和白蛋白尿以及肾脏 ANG II 和 ET-1 水平的影响。3 个月大的雄性 Ren-2 转基因大鼠 (TGR) 分别用氯沙坦 (5mg/kg/d) 或阿利克仑 (10mg/kg/d) 治疗 10 周。实验结束时，大鼠断头取血，分离皮质和乳头部分肾脏。通过 RIA 测量血浆和组织 ANG II 水平，通过 ELISA 测量组织 ET-1 浓度。在所有四组动物中，ET-1 水平在肾脏皮质中最低，在乳头中高 100 多倍。未经处理的 TGR 的皮质和乳头 ET-1 浓度明显高于 HanSD 对照大鼠，并且这两种药物都明显降低。在两种品系中，乳头 ANG II 浓度略高但明显高于皮质 ANG II，TGR 显示出比 HanSD 对照大鼠更高的皮质和乳头 ANG II 水平。阿利克仑和氯沙坦在所用剂量下同样降低皮质和乳头 ANG II 水平，并使 HanSD 大鼠的肾皮质和乳头 ET-1 明显低于对照水平。白蛋白尿在 TGR 中的水平是 HanSD 大鼠的两倍多，阿利克仑使其正常化，氯沙坦使其降低 28%，尽管 MAP 被这两种药物降低到相似的程度。尽管 MAP 和肾脏 ET-1 和 ANG II 水平的降低相似，但阿利克仑在降低杂合高血压 Ren-2 大鼠的白蛋白尿方面似乎比氯沙坦更有效，在所用剂量下。
