Submitted on December 9, 2008
Revised on January 27, 2009
Accepted on January 27, 2009
ROSIGLITAZONE DECREASES BLOOD PRESSURE AND RENAL INJURY IN A FEMALE MOUSE MODEL OF SYSTEMIC LUPUS ERYTHEMATOSUS
Marcia R. Venegas-Pont1, Julio C Sartori-Valinotti1, Christine Maric2, Lorraine C Racusen3, Porter H. Glover1, Gerald R McLemore, Jr.1, Allison V. Jones1, Jane F. Reckelhoff1, and Michael J Ryan1*
1 University of Mississippi Medical Center
2 University of Mississippi
3 Johns Hopkins University Medical Center
* To whom correspondence should be addressed. E-mail: mjryan{at}physiology.umsmed.edu.
Women with Systemic Lupus Erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPAR
) agonist, has renal protective and anti-hypertensive effects. We tested whether Rosi ameliorates hypertension and renal injury in a female mouse model of SLE (NZBWF1). Thirty week old SLE and control (NZW/LacJ) mice (n
6/group) were fed Rosi (5mg/kg/day in standard chow) or standard chow for four weeks. SLE mice had increased blood pressure (BP in mmHg) compared to controls (139±4 vs. 111±4, p<0.05). Rosi treatment lowered BP in SLE mice (127±4, p<0.05) but not in controls (111±4). Urinary albumin (µg/mg creatinine) was increased in SLE mice compared to controls (12396±6525 vs. 50±6) and reduced with Rosi treatment (148±117). Glomerulosclerosis (% of glomeruli with sclerosis) was reduced in Rosi treated SLE mice (4.2±1.6 vs. 0.4±0.3, p<0.05). Renal monocyte/macrophage numbers (cell number/ 1320 points counted) were reduced in SLE mice treated with Rosi (32.6±11.0 vs. 10.6±3.6, p<0.05) but unchanged in controls (3.7±1.6 vs. 3.7±2.0). Renal osteopontin expression, a cytokine regulating macrophage recruitment, was reduced in Rosi treated SLE mice. Urinary endothelin (in pg/mg creatinine) was increased in SLE mice compared to controls (1.9±0.59 vs. 0.6±0.04, p<0.05) and reduced in SLE mice treated with Rosi (0.8±0.11, p<0.05). PPAR protein expression in the renal cortex was significantly lower in SLE mice compared to controls and was unaffected by Rosi. These data suggest that Rosi may be an important therapeutic option for the treatment of SLE hypertension and renal injury.
