Aldosterone antagonism ameliorates proteinuria and nephrosclerosis independent of glomerular dynamics in L-NAME/SHR model

Am J Nephrol. Mar-Apr 2004;24(2):242-9. doi: 10.1159/000077396. Epub 2004 Mar 17.

Abstract

Background: The renin-angiotensin-aldosterone system participates importantly in the progression of hypertensive renal disease. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists have been demonstrated to afford renoprotection in L-NAME-exacerbated nephrosclerosis in SHR rats. This study was designed to examine the effects of the aldosterone antagonist eplerenone on systemic and renal hemodynamics, glomerular dynamics, renal function and histopathology in L-NAME/SHR, and determine whether aldosterone antagonism would enhance the effectiveness of ACE inhibition.

Methods: Six groups of 20-week-old SHR were studied using renal micropuncture and histopathological techniques after 3 weeks of treatment: SHR control (tapwater, n = 10); SHR + eplerenone (101 +/- 8.3 mg/kg/day, n = 10); SHR + L-NAME (5.0 +/- 0.12 mg/kg/day, n = 9); SHR + L-NAME + eplerenone (n = 8); SHR + L-NAME + lisinopril (3 mg/kg/day, n = 9), and SHR + L-NAME + eplerenone + lisinopril (n = 9).

Results: L-NAME-treated SHR developed massive proteinuria, severe hypertensive nephrosclerosis, and tubulointerstitial damage. Eplerenone significantly reduced proteinuria (127.4 +/- 26.5 vs. 51.9 +/- 16.7 mg/24 h, p < 0.01), improved glomerular and arteriolar injuries (65 +/- 9 vs. 29 +/- 9 score/100 glomeruli, p < 0.01; 116 +/- 18 vs. 41 +/- 13 score/100 arterioles, p < 0.01, respectively), and decreased tubulointerstitial damage index (1.43 +/- 0.07 vs. 0.39 +/- 0.07, p < 0.01) without altering mean arterial pressure or glomerular dynamics. Combined therapy of eplerenone with lisinopril produced no further benefits than lisinopril alone.

Conclusion: The aldosterone antagonist eplerenone significantly ameliorated proteinuria and nephrosclerosis in the L-NAME/SHR model, independent of hemodynamic effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Eplerenone
  • Hemodynamics / drug effects
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiopathology
  • Male
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nephrosclerosis / drug therapy*
  • Nephrosclerosis / pathology
  • Proteinuria / drug therapy*
  • Rats
  • Rats, Inbred SHR
  • Spironolactone / analogs & derivatives*
  • Spironolactone / therapeutic use*

Substances

  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone
  • NG-Nitroarginine Methyl Ester