PT  - JOURNAL ARTICLE
AU  - Pérez  de Lema, Guillermo
AU  - de Wit, Cor
AU  - Cohen, Clemens D.
AU  - Nieto, Elena
AU  - Molina, Ana
AU  - Banas, Bernhard
AU  - Luckow, Bruno
AU  - Vicente, Ana B.
AU  - Mampaso, Francisco
AU  - Schlöndorff, Detlef
TI  - Angiotensin Inhibition Reduces Glomerular Damage and Renal Chemokine Expression in MRL/lpr Mice
AID  - 10.1124/jpet.103.053678
DP  - 2003 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 275--281
VI  - 307
IP  - 1
4099  - http://jpet.aspetjournals.org/content/307/1/275.short
4100  - http://jpet.aspetjournals.org/content/307/1/275.full
SO  - J Pharmacol Exp Ther2003 Oct 01; 307
AB  - Beneficial effects of angiotensin II inhibition during inflammatory renal disease may involve both hemodynamic and nonhemodynamic mechanisms. To analyze whether angiotensin II inhibition has protective effects on lupus-like, autoimmune-mediated renal damage in MRL/lpr mice, four groups of mice were treated orally for 6 weeks with: 1) vehicle, 2) enalapril (3.0 mg/kg per day), 3) candesartan cilexetil (5.0 mg/kg), or 4) amlodipine (10 mg/kg) as a blood pressure control (n = 9–12/group). All antihypertensive treatments lowered blood pressure to a similar level compared with vehicle group (enalapril: 99.8 ± 8.3 mm Hg; candesartan: 101 ± 9 mm Hg; amlodipine: 103.8 ± 6.7 mm Hg; vehicle: 113.5 ± 4.6 mm Hg). Vehicle-treated mice developed a moderate glomerular injury with albuminuria (35.1 ± 39.0 μg/mg of creatinine). Glomerular lesions consisted of immune complex deposition and mesangial expansion with increased mesangial cell proliferation. Amlodipine treatment had no significant protective effects. In contrast to vehicle- and amlodipine-treated mice, those subjected to angiotensin II blockade with enalapril or candesartan had reduced albuminuria, glomerular expansion, and mesangial proliferation. This was associated with significantly reduced renal chemokine mRNA expression compared with vehicle treatment. Our results show that inhibition of angiotensin II has protective effects on the glomerular damage of MRL/lpr mice that extend beyond hemodynamics and involve down-modulation of glomerular inflammation, reduction of mesangial cell proliferation, and decrease in chemokine expression. The American Society for Pharmacology and Experimental Therapeutics