Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria 3081, Australia.
Clin Sci (Lond). 2011 Apr;120(8):335-45. doi: 10.1042/CS20100280.
ACE (angiotensin-converting enzyme) 2 is expressed in the heart and kidney and metabolizes Ang (angiotensin) II to Ang-(1-7) a peptide that acts via the Ang-(1-7) or mas receptor. The aim of the present study was to assess the effect of Ang-(1-7) on blood pressure and cardiac remodelling in a rat model of renal mass ablation. Male SD (Sprague-Dawley) rats underwent STNx (subtotal nephrectomy) and were treated for 10 days with vehicle, the ACE inhibitor ramipril (oral 1 mg·kg(-1) of body weight·day(-1)) or Ang-(1-7) (subcutaneous 24 μg·kg(-1) of body weight·h(-1)) (all n = 15 per group). A control group (n = 10) of sham-operated rats were also studied. STNx rats were hypertensive (P<0.01) with renal impairment (P<0.001), cardiac hypertrophy (P<0.001) and fibrosis (P<0.05), and increased cardiac ACE (P<0.001) and ACE2 activity (P<0.05). Ramipril reduced blood pressure (P<0.01), improved cardiac hypertrophy (P<0.001) and inhibited cardiac ACE (P<0.001). By contrast, Ang-(1-7) infusion in STNx was associated with further increases in blood pressure (P<0.05), cardiac hypertrophy (P<0.05) and fibrosis (P<0.01). Ang-(1-7) infusion also increased cardiac ACE activity (P<0.001) and reduced cardiac ACE2 activity (P<0.05) compared with STNx-vehicle rats. Our results add to the increasing evidence that Ang-(1-7) may have deleterious cardiovascular effects in kidney failure and highlight the need for further in vivo studies of the ACE2/Ang-(1-7)/mas receptor axis in kidney disease.
ACE（血管紧张素转换酶）2 在心脏和肾脏中表达，并将 Ang（血管紧张素）II 代谢为 Ang-（1-7）肽，该肽通过 Ang-（1-7）或 mas 受体发挥作用。本研究旨在评估 Ang-（1-7）对肾切除大鼠模型血压和心脏重构的影响。雄性 SD（Sprague-Dawley）大鼠接受 STNx（部分肾切除术），并接受 10 天的载体、ACE 抑制剂雷米普利（口服 1mg·kg-1·体重·天-1）或 Ang-（1-7）（皮下 24μg·kg-1·体重·h-1）（每组 n = 15）治疗。还研究了一组 10 只假手术对照大鼠。STNx 大鼠血压升高（P<0.01），伴有肾功能损害（P<0.001）、心脏肥大（P<0.001）和纤维化（P<0.05），以及心脏 ACE（P<0.001）和 ACE2 活性增加（P<0.05）。雷米普利降低血压（P<0.01），改善心脏肥大（P<0.001），抑制心脏 ACE（P<0.001）。相比之下，Ang-（1-7）输注与 STNx 大鼠血压进一步升高（P<0.05）、心脏肥大（P<0.05）和纤维化（P<0.01）相关。Ang-（1-7）输注还增加了心脏 ACE 活性（P<0.001），降低了心脏 ACE2 活性（P<0.05），与 STNx-载体大鼠相比。我们的研究结果进一步证明，在肾衰竭中，Ang-（1-7）可能具有有害的心血管作用，并强调需要进一步研究 ACE2/Ang-（1-7）/mas 受体轴在肾脏疾病中的作用。
