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November 19, 2010Clinical Science74 citationsOpen Access

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

EVElena VelkoskaRDRachael DeanKGKaren Griggs

Key Result

In rats with subtotal nephrectomy, Ang-(1-7) infusion was associated with further increases in blood pressure (P<0.05), cardiac hypertrophy (P<0.05), and fibrosis (P<0.01) compared to vehicle.

Key Points

  • This study aims to analyze the effects of angiotensin-(1-7) on blood pressure and cardiac remodelling in a rat model with renal impairment.
  • Male Sprague-Dawley rats underwent subtotal nephrectomy (n=15 per group) and treated with vehicle, ramipril, or angiotensin-(1-7) for 10 days.
  • A control group of sham-operated rats was included (n=10) for comparison.
  • Subtotal nephrectomy rats exhibited increased blood pressure (P<0.01) and cardiac hypertrophy (P<0.001).
  • Ang-(1-7) infusion led to further increased blood pressure (P<0.05) and cardiac fibrosis (P<0.01).
  • Ang-(1-7) infusion increased cardiac ACE activity (P<0.001) compared to vehicle-treated STNx rats.

Structured PICO

Does Ang-(1-7) infusion improve blood pressure and cardiac remodelling in a rat model of subtotal nephrectomy?

P
Population
55 male Sprague-Dawley rats with subtotal nephrectomy treated for 10 days.
I
Intervention
Ang-(1-7) subcutaneous 24 μg·kg(-1) of body weight·h(-1) for 10 days
C
Comparator
Vehicle or ramipril (oral 1 mg·kg(-1) of body weight·day(-1)) for 10 days
O
Outcome
Blood pressure and cardiac remodelling (cardiac hypertrophy and fibrosis)surrogate

In a rat model of renal mass ablation, Ang-(1-7) infusion worsened blood pressure and adverse cardiac remodeling, suggesting potential deleterious cardiovascular effects in kidney failure.

Main Result

p-value: p=<0.05

Abstract

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.

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Cite This Study

Velkoska et al. (2010) studied Renal mass ablation (subtotal nephrectomy) (n=55). Ang-(1-7) vs. vehicle was evaluated on Blood pressure and cardiac remodelling (p=<0.05). In rats with subtotal nephrectomy, Ang-(1-7) infusion was associated with further increases in blood pressure (P<0.05), cardiac hypertrophy (P<0.05), and fibrosis (P<0.01) compared to vehicle.

synapsesocial.com/papers/6a430e4dfa4e591276380e50https://doi.org/10.1042/cs20100280
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