Angiotensin-Converting Enzyme Inhibitor (ACEI)-Mediated Amelioration in Renal Fibrosis Involves Suppression of Mast Cell Degranulation.

BACKGROUND/AIMS The mechanism by which angiotensin-converting enzyme inhibitors (ACEIs) attenuate renal fibrosis has not been fully uncovered. METHODS Renal fibrosis in rats was triggered by unilateral ureteral obstruction (UUO) and treated with Enalapril. RESULTS Enalapril attenuated renal fibrosis, as evidenced by the fibrosis scores (1.07±0.73 versus 2.18±0.75 for 200 mg/ml Enalapril versus control, p<0.01) of Enalapril-treated UUO rats compared to mock-treated UUO rats. The amelioration was mast cell dependent, as Enalapril exhibited no effects on mast cell-deficient Kit(wsh/wsh) mice developing renal fibrosis. We detected lower levels of transforming growth factor β (TGF-β) and alpha-smooth muscle actin (α-SMA, a fibroblast activation marker) in the kidney tissue of Enalapril-treated UUO rats relative to the control UUO rats. Enalapril-treated UUO rats exhibited far fewer mast cells infiltrating per area in the kidney tissue than the control UUO rats (8.00±0.65 versus 29.00±0.57, p<0.01). Electron microscopy images revealed that mast cell degranulation was inhibited by Enalapril treatment. Further, IgE-mediated passive cutaneous anaphylaxis demonstrated that Enalapril blocked mast cell degranulation in vivo. CONCLUSION Enalapril attenuated renal fibrosis in UUO rats, possibly by a mechanism involving the suppression of mast cell degranulation.