Imidapril improves l-NAME-exacerbated nephrosclerosis with TGF-β1 inhibition in spontaneously hypertensive rats

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Abstract

Objective

This study was designed to investigate whether chronic angiotensin-converting enzyme (ACE) inhibition prevents hypertensive glomerular injury and inhibits increases in the mRNA levels and immunohistological expression of the apoptosis inducer caspase-3, and transforming growth factor (TGF)-β1 during prolonged nitric oxide synthase (NOS) inhibition with NG-nitro-l-arginine methyl ester (l-NAME) in spontaneously hypertensive rats (SHR).

Methods and results

For 3 weeks, we studied three groups of 20-week-old male SHR: a control group, a l-NAME group, and a group treated with l-NAME and the ACE inhibitor imidapril. l-NAME rats developed severe hypertensive nephrosclerosis with significantly elevated blood pressure, markedly increased urinary protein excretion and serum creatinine levels, and more severe glomerulosclerosis and tubulo-interstitial changes. Levels of TGF-β1 mRNA in the renal tissue was also significantly increased in l-NAME rats compared with control SHR. Addition of imidapril significantly lowered blood pressure, inhibited nephrosclerosis and attenuated the mRNA level of TGF-β1 in comparison with l-NAME/SHR. Histologically, the glomerular cell apoptosis labeling index, terminal doxynucleotidil transferase-mediated dUTP nick-end labeling of fragmented DNA (TUNEL) and active caspase-3, and TGF-β1 positive areas were also reduced by imidapril.

Conclusion

These data suggest that imidapril prevents glomerular and arteriolar damages and renal functions, through inhibiting both TGF-β1 production and apoptosis induction.

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