Back to Search
Start Over
Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats.
- Source :
-
Kidney international [Kidney Int] 2003 May; Vol. 63 (5), pp. 1791-800. - Publication Year :
- 2003
-
Abstract
- 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.<br />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).<br />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).<br />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.
- Subjects :
- Animals
Blood Pressure
Cytokines metabolism
Eplerenone
Fibrosis
Hypertension, Renal drug therapy
Hypertension, Renal pathology
Immunohistochemistry
In Situ Hybridization
Kidney immunology
Kidney pathology
Macrophages pathology
Male
Nephritis pathology
Rats
Rats, Sprague-Dawley
Spironolactone pharmacology
Aldosterone pharmacology
Hypertension, Renal immunology
Nephritis chemically induced
Nephritis immunology
Sodium Chloride pharmacology
Spironolactone analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0085-2538
- Volume :
- 63
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 12675855
- Full Text :
- https://doi.org/10.1046/j.1523-1755.2003.00929.x