Angiotensin-(1-7) infusion is associated with increased blood pressure and adverse cardiac remodelling in rats with subtotal nephrectomy

作者：Velkoska Elena; Dean Rachael G; Griggs Karen; Burchill Luke; Burrell Louise M^*

来源：Clinical Science, 2011, 120(7-8): 335-345.

DOI：10.1042/CS20100280

• angiotensin peptide
• cardiac fibrosis
• kidney failure
• renal mass reduction
• renin-angiotensin system

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 mu g . 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.

• 出版日期2011-4