Why the study?
Does enalapril reduce renal fibrosis in rats with unilateral ureteral obstruction?
Does enalapril reduce renal fibrosis in rats with unilateral ureteral obstruction?
Enalapril attenuates renal fibrosis in a UUO rat model, likely through a mechanism involving the suppression of mast cell degranulation.
Provides preclinical support for enalapril in renal fibrosis; leaves open clinical translation.
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.
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Sun et al. (2016) studied this question.
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