PMID- 12675855
OWN - NLM
STAT- MEDLINE
DCOM- 20031217
LR  - 20181130
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 63
IP  - 5
DP  - 2003 May
TI  - Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats.
PG  - 1791-800
AB  - BACKGROUND: We evaluated the role of aldosterone as a mediator of renal 
      inflammation and fibrosis in a rat model of aldosterone/salt hypertension using 
      the selective aldosterone blocker, eplerenone. METHODS: Unnephrectomized, 
      Sprague-Dawley rats were given 1% NaCl (salt) to drink and randomized to receive 
      treatment for 28 days: vehicle infusion (control); 0.75 microg/hour aldosterone 
      subcutaneous infusion; or aldosterone infusion + 100 mg/kg/day oral dose of 
      eplerenone. Blood pressure and urinary albumin were measured and kidneys were 
      evaluated histologically. Renal injury, inflammation, and fibrosis were assessed 
      by immunohistochemistry, in situ hybridization, and reverse 
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Aldosterone/salt 
      induced severe hypertension compared to controls (220 +/- 4 mm Hg vs. 131 +/- 4 
      mm Hg, P < 0.05), which was partially attenuated by eplerenone (179 +/- 4 mm Hg, 
      P < 0.05). In aldosterone/salt treated rats, renal histopathologic evaluation 
      revealed severe vascular and glomerular sclerosis, fibrinoid necrosis and 
      thrombosis, interstitial leukocyte infiltration, and tubular damage and 
      regeneration. Aldosterone/salt increased circulating osteopontin (925.0 +/- 80.2 
      ng/mL vs. 53.6 +/- 6.3 ng/mL) and albuminuria (75.8 +/- 10.9 mg/24 hours vs. 13.2 
      +/- 3.0 mg/24 hours) compared to controls and increased expression of 
      proinflammatory molecules. Treatment with eplerenone reduced systemic osteopontin 
      (58.3 +/- 4.2 ng/mL), albuminuria (41.5 +/- 7.2 mg/24 hours), and proinflammatory 
      gene expression: osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), 
      interleukin-6 (IL-6), and interleukin-1beta (IL-1beta). CONCLUSION: These 
      findings indicate that aldosterone/salt-induced renal injury and fibrosis has 
      inflammatory components involving macrophage infiltration and cytokine 
      up-regulation. Attenuation of renal damage and inflammation by eplerenone 
      supports the protective effects of aldosterone blockade in hypertensive renal 
      disease.
FAU - Blasi, Eileen R
AU  - Blasi ER
AD  - Pharmacia Corporation, Cardiovascular and Metabolic Diseases, Global Medical 
      Affairs, and Global Toxicology, St. Louis, Missouri 63167, USA.
FAU - Rocha, Ricardo
AU  - Rocha R
FAU - Rudolph, Amy E
AU  - Rudolph AE
FAU - Blomme, Eric A G
AU  - Blomme EA
FAU - Polly, Melissa L
AU  - Polly ML
FAU - McMahon, Ellen G
AU  - McMahon EG
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Cytokines)
RN  - 27O7W4T232 (Spironolactone)
RN  - 451W47IQ8X (Sodium Chloride)
RN  - 4964P6T9RB (Aldosterone)
RN  - 6995V82D0B (Eplerenone)
SB  - IM
MH  - Aldosterone/*pharmacology
MH  - Animals
MH  - Blood Pressure
MH  - Cytokines/metabolism
MH  - Eplerenone
MH  - Fibrosis
MH  - Hypertension, Renal/drug therapy/*immunology/pathology
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Kidney/immunology/pathology
MH  - Macrophages/pathology
MH  - Male
MH  - Nephritis/*chemically induced/*immunology/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium Chloride/*pharmacology
MH  - Spironolactone/*analogs & derivatives/pharmacology
EDAT- 2003/04/05 05:00
MHDA- 2003/12/18 05:00
CRDT- 2003/04/05 05:00
PHST- 2003/04/05 05:00 [pubmed]
PHST- 2003/12/18 05:00 [medline]
PHST- 2003/04/05 05:00 [entrez]
AID - S0085-2538(15)49069-6 [pii]
AID - 10.1046/j.1523-1755.2003.00929.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 May;63(5):1791-800. doi: 10.1046/j.1523-1755.2003.00929.x.