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The influence of aldosterone and angiotensin II on the diuretic effects of atrial natriuretic peptide in the isolated perfused rat kidney

Background

The diuretic effects of atrial natriuretic peptide (ANP-99-126) are reduced in patients with advanced cirrhosis of the liver and severe myocardial dysfunction. These patients also often display an increased acitivity of the renin-angiotensin-aldosterone system (RAAS) resulting in high plasma concentrations of aldosterone (ALD) and angiotensin II (AII).

Objective

To study the effects of ANP in isolated perfused rat kidneys after pretreatment with AII or ALD to determine which hormone causes ANP unresponsiveness in this setting.

Materials and methods

Three groups of kidneys were perfused for 3 h with a constant perfusion pressure of 100 mmHg.: a control group (n = 5), a AII/ANP group (n = 6; 0.1 nmol/l AII in the second hour; 3.25 nmol/l hANP in the third hour) and an ALD/ANP group (n = 4; 27.7 nmol/l ALD in the second hour; 3.25 nmol/l hANP in the third hour). We determined urine flow (VU), urinary excretion of sodium (VNaU) and potassium (VkU), inulin-clearance (GFR) and renal vascular resistance RVR.

Results

AII/ANP group: treatment with AII decreased VU, VNaU, VkU and GFR and increased RVR. ANP restored renal function to control levels (VNaU, VkU, GFR) or above (VU, RVR). ALD/ANP group: treatment with ALD induced an increase of VkU. Subsequent treatment with ANP further increased VkU and slightly decreased RVR. No effects on GFR, VU or VNaU were observed.

Conclusion

Our findings suggest that blunted ANP effects during increased RAAS-activity are mainly determined by ALD. Interestingly, this is not only due to a blunted increase of sodium excretion (tubular mechanism) but also due to a blunted increase of glomerular filtration rate (altered glomerular vascular reactivity).

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Heringlake, M., Wagner, K., Schumach, J. et al. The influence of aldosterone and angiotensin II on the diuretic effects of atrial natriuretic peptide in the isolated perfused rat kidney. Crit Care 3, P206 (2000). https://doi.org/10.1186/cc579

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Keywords

  • Glomerular Filtration Rate
  • Aldosterone
  • Glomerular Filtration
  • Perfusion Pressure
  • Atrial Natriuretic Peptide