Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus.
Women with systemic lupus erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPARgamma) agonist, has renal protective and antihypertensive 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 > or = 6/group) were fed Rosi (5 mg.kg(-1).day(-1) in standard chow) or standard chow for 4 wk. SLE mice had increased blood pressure (BP in mmHg) compared with 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 (mug/mg creatinine) was increased in SLE mice compared with controls (12,396 +/- 6,525 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/1,320 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 with 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). PPARgamma protein expression in the renal cortex was significantly lower in SLE mice compared with 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.
Venegas-Pont
Marcia
M
Assistant Professor, Univ. of Mississippi Medical Center, Dept. of Physiology & Biophysics, 2500 North State St., Jackson, MS 39216-4505. mjryan@physiology.umsmed.edu.
Sartori-Valinotti
Julio C
JC
Maric
Christine
C
Racusen
Lorraine C
LC
Glover
Porter H
PH
McLemore
Gerald R
GR
Jones
Allison V
AV
Reckelhoff
Jane F
JF
Ryan
Michael J
MJ
D000419:Albuminuria / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000235:genetics; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000652:urine; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D053495:Osteopontin / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D000959:Antihypertensive Agents; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019332:Endothelin-1; D047495:PPAR gamma; D012333:RNA, Messenger; C506896:Spp1 protein, mouse; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D053495:Osteopontin