The angiotensin receptor antagonist, irbesartan, reduces renal injury in experimental chronic renal failure

Kidney Int Suppl. 1996 Dec:57:S132-6.

Abstract

The effects of chronic treatment with the specific AT1 angiotensin receptor antagonist, irbesartan, or the angiotensin converting enzyme inhibitor, enalapril, were assessed in uninephrectomized fawn-hooded hypertensive rats (FHH) and compared with vehicle treatment. Three days after uninephrectomy, irbesartan (240 mg/liter), enalapril (80 mg/liter) or vehicle were administered via the drinking water. Systolic blood pressure (SBP) and protein excretion rates (UprotV) were determined monthly. In rats receiving irbesartan (N = 7) and enalapril (N = 6) SBP (132 +/- 3 mm Hg and 133 +/- 6, respectively) was essentially normalized at 12 weeks when compared with vehicle (169 +/- 6 mm Hg (N = 6); all comparisons were P < 0.05 by ANOVA). Similarly, proteinuria was lower in irbesartan (44 +/- 12 mg/day) and enalapril (19 +/- 2) groups versus vehicle (123 +/- 10 mg/day). Treatment with both drugs was associated with marked reduction in glomerulosclerosis at 12 weeks (both < 5% vs. vehicle, 43 +/- 9%) without effect on glomerular volume. In identically prepared rats, glomerular capillary hydraulic pressure (PGC, estimated from stop-flow pressure, Psf) was lower in FHH receiving irbesartan (58 +/- 1 mm Hg, N = 6) or enalapril (54 +/- 2, N = 6) than in vehicle-treated rats, in whom PGC was greatly elevated (68 +/- 2 mm Hg; N = 7). Despite this, GFR and single nephron GFR were well maintained. These data support a critical role for AT1 receptor-mediated, angiotensin-dependent processes in the pathogenesis of hypertension in FHH, and further implicate elevated PGC as a major determinant of glomerular injury in this model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Biphenyl Compounds / pharmacology*
  • Blood Pressure / drug effects*
  • Enalapril / pharmacology*
  • Irbesartan
  • Kidney Failure, Chronic / drug therapy
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / physiopathology
  • Nephrectomy
  • Proteinuria / prevention & control*
  • Rats
  • Rats, Inbred SHR
  • Tetrazoles / pharmacology*

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Biphenyl Compounds
  • Tetrazoles
  • Enalapril
  • Irbesartan