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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 VelkoskaCSL (Australia)RDRachael DeanQuadram InstituteKGKaren GriggsLa Trobe University

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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