Korean J Nephrol.  1999 Nov;18(6):877-886.

Effects of Individual or Combined Treatment with Enalapril and Lovastatin on the Osteopontin Gene Expression in 5/6 Nephrectomized Rats

• Kim SB
• Park JS
• Yang WS
• Park SK
• Lee SK
• Lee JS

Abstract

Osteopontin, a secreted, arginine-glycin-asparate (RGD)-containing phosphoprotein is up-regulated in renal cortex in many experimental models of tubu- lointerstitial fibrosis. Osteopontine gene seems to be induced predominantly in chronic and progressive glomerulosclerosis. To examine the effects of enala-pril and lovastatin alone or in combination on osteopontin, TGF- 8, endothelin- 1, procollagen a 1(I) at an early phase of chronic renal failure in 5/6 nephrectomized rats, randomly assigned 4 groups [untreated 5/6 nephrectomy(group Nx), treated with enalapril(group E) or lovastatin(group L) alone and in combination(group EL)(each group n=6)] were sacrificed at 8 weeks. Four rats were served as normal control ones. Systolic blood pressure, 24 hour urine protein excretion, serum chemistry were mea- sured. mRNA levels of renal cortical osteopontin, TGF- , endothelin-l, procollagen a 1(I) were measured by Northern hybridization. Eight week after nephrectomy untreated neph- rectomized rats had higher systemic blood pressure (157 3 vs. 140 1mmHg, p<0.05) with increasing proteinuria(32.9 11 vs. 1.2 0.2, p<0.05) than normal con- trol rats. mRNA expression of osteopontin(12.5 folds, p<0.05) and endothelin-l(1.6 folds, p<0.05) in renal cortex were elevated, but mRNA expression of TGF- 0 and procollagen a 1(I) were not. The treatment with enalapril or lovastatin alone prevented a further rise in proteinuria and significantly reduced renal cortical osteopontin mRNA expression at 8 weeks. Enalapril reversed systemic hypertension but lovastatin not. Both drugs had no effect on renal cortical endothelin-1 mRNA expression. The treatment with combined enalapril and lovastatin reduced renal cortical osteopontin mRNA expression more and showed trend to reduce proteinuria compared to treatment with each drug alone. The results of the present study indicate that the treatment with enalapril or lovastatin reduces proteinuria and renal cortical osteopontin mRNA expression which are occurred at early phase of chronic renal failure in 5/6 nephrectomized rat model and combined treatment appears to be more effective.

MeSH Terms

Animals
Blood Pressure
Chemistry
Enalapril*
Endothelin-1
Fibrosis
Gene Expression*
Hypertension
Kidney Failure, Chronic
Lovastatin*
Models, Animal
Models, Theoretical
Nephrectomy
Osteopontin*
Procollagen
Proteinuria
Rats*
RNA, Messenger
Enalapril
Endothelin-1
Lovastatin
Osteopontin
Procollagen
RNA, Messenger