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

AbstractBACKGROUND:
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.
AuthorsXiaoyan Zhou, Hidehiko Ono, Yuko Ono, Edward D Frohlich
JournalAmerican journal of nephrology (Am J Nephrol) 2004 Mar-Apr Vol. 24 Issue 2 Pg. 242-9 ISSN: 0250-8095 [Print] Switzerland
PMID15031627 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2004 S. Karger AG, Basel
Chemical References
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Eplerenone
  • Hemodynamics (drug effects)
  • Kidney Glomerulus (drug effects, pathology, physiopathology)
  • Male
  • Mineralocorticoid Receptor Antagonists (therapeutic use)
  • NG-Nitroarginine Methyl Ester (pharmacology)
  • Nephrosclerosis (drug therapy, pathology)
  • Proteinuria (drug therapy)
  • Rats
  • Rats, Inbred SHR
  • Spironolactone (analogs & derivatives, therapeutic use)

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