RT Journal Article
SR Electronic
T1 Angiotensin Inhibition Reduces Glomerular Damage and Renal Chemokine Expression in MRL/lpr Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 275
OP 281
DO 10.1124/jpet.103.053678
VO 307
IS 1
A1 Guillermo Pérez  de Lema
A1 Cor de Wit
A1 Clemens D. Cohen
A1 Elena Nieto
A1 Ana Molina
A1 Bernhard Banas
A1 Bruno Luckow
A1 Ana B. Vicente
A1 Francisco Mampaso
A1 Detlef Schlöndorff
YR 2003
UL http://jpet.aspetjournals.org/content/307/1/275.abstract
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