(Hypertension. 1999;33:225-231.)
© 1999 American Heart Association, Inc.
Scientific Contribution |
Enalapril Prevents Tubulointerstitial Lesions by Hyperoxaluria
Correspondence to Jorge E. Toblli, MD, PhD, Laboratory of Experimental Medicine, Department of Internal Medicine, Hospital Alemán, Av. Pueyrredon 1640, Buenos Aires (1118) Argentina. E-mail jtoblli{at}pinos.com
Abstract—Hyperoxaluria is
a recognized cause of tubulointerstitial lesions,
and this could contribute to development of hypertension and chronic
renal failure. Enalapril has been effective against the progression of
tubulointerstitial lesions in various animal
models. The aim of the present study was to evaluate the usefulness
of enalapril on the tubulointerstitial damage
produced by oxalates. Two-month-old male Sprague-Dawley rats were
separated into 4 groups, control with tap water (G1), hyperoxaluric
(G2), hyperoxaluric+enalapril (G3), enalapril (G4), for 4 weeks. G2 and
G3 rats were given 1% ethyleneglycol (ETG, precursor for oxalates),
and G3 and G4 rats were given enalapril 20 mg/L in drinking
water. At the end of the study, we evaluated renal
tubulointerstitial lesions by a semiquantitative
score. Urine albumin excretion, serum and urine nitric oxide
production, tubulointerstitial
immunostaining by 
-smooth muscle actin, transforming
growth factor-ß1, and collagen type III were measured.
Rats belonging to the hyperoxaluric group treated with enalapril (G3)
showed fewer tubulointerstitial lesions (1.3±0.2
versus 3±0.2; P<0.01), lower urine albumin
excretion (8±2 mg/d versus 25±2 mg/d; P<0.01), less
percentage of -smooth muscle actin in renal interstitium (2±0.4%
versus 13.5±2.4%; P<0.01), less percentage of
transforming growth factor-ß1 in
tubulointerstitial area (3.3±1% versus
13.3±2.1%; P<0.01), less percentage of collagen type
III interstitial deposition (0.7±0.5% versus 7±2.6%;
P<0.01), and increased NO production in serum
as well as urine (both P<0.01), when compared with the
hyperoxaluric group not treated with enalapril (G2). Considering these
data, we believe that enalapril, by several mechanisms of action, could
provide an important benefit in the prevention of inflammatory
response, transforming growth factor-ß1
tubulointerstitial production, collagen
type III interstitial deposition, and finally, the
progressive tubulointerstitial fibrosis caused
by oxalates.
Key Words: enalapril • hyperoxaluria • tubulointerstitial lesions • renal fibrosis • renin-angiotensin system.
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