Renal vascular structural properties and their alterations by removal of uraemic toxins in a rat model of chronic kidney disease

Clin Exp Pharmacol Physiol. 2014 Mar;41(3):238-45. doi: 10.1111/1440-1681.12208.

Abstract

1. Renal vascular structural properties and their alterations by removal of uraemic toxins with AST-120, an oral adsorbent, were examined in subtotal nephrectomized rats. 2. Eight- or 9-week-old Sprague-Dawley rats received 3/4 nephrectomy (n = 18) and thereafter were fed 24.5% protein diet with (AST; n = 9) or without (AST-; n = 9) AST-120 (0.4 g/100 g bodyweight). Sham-operated rats (Sham; n = 9) received the diet without AST-120. At 21-22 weeks of age, flow-pressure (F-P) and pressure-glomerular filtration rate (P-GFR) relationships were determined for maximally vasodilated, perfused kidneys. 3. The gradient of F-P (minimal renal vascular resistance reflecting the overall luminal dimensions of pre- and post-glomerular vasculature) was lower in AST- than Sham rats. In contrast, the x-intercept (preglomerular : post-glomerular vascular resistance ratio) and gradient (glomerular filtration capacity) of P-GFR did not differ between the two groups. The vascular wall and lumen at the interlobular arteries were greater in AST- than Sham rats. 4. Although the vascular wall and lumen at the interlobular arteries were less in AST than in AST- rats, the gradient of F-P and the x-intercept of P-GFR did not differ between the two groups. In contrast, the glomerular filtration capacity was greater in AST than AST- rats. 5. In conclusion, the lumen of both pre- and post-glomerular resistance vessels increased and glomerular filtration capacity failed to increase in subtotal nephrectomized rats. Uraemic toxins could play an important role in the development of structural alterations in glomeruli rather than renal resistance vessels in chronic kidney disease.

Keywords: chronic kidney disease; oral adsorbent AST-120; renal vascular structure; subtotal nephrectomized rats; uraemic toxins.

MeSH terms

  • Animals
  • Blood Pressure / physiology
  • Carbon / pharmacology
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / physiopathology*
  • Male
  • Nephrectomy / methods
  • Oxides / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency, Chronic / physiopathology*
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology
  • Vasodilation / physiology

Substances

  • Oxides
  • Carbon
  • AST 120