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KMID : 0350519950480040989
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Journal of Catholic Medical College
1995 Volume.48 No. 4 p.989 ~ p.1001
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Effect of Enalapril on Chronic Cyclosporine Nephropathy
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Abstract
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It has been reported that cyclosporin A (CsA) stimulates renin-angiotensin-aldosterone system (RAS), but it is controversial whether activation of this system is associated with CsA nephrotoxicity or not. Therefore, we performed this study to
evaluate
the effect of enalapril (ENAP), an angiotensin converting enzyme inhibitor, on the renal function in chronic CsA nephropathy. After unilateral nephrectomy, following three groups were studied : 1) Control group (rats treated with vehicle, n=10),
2)
CsA
group (rats treated with CsA, n=10), 3) ENAP group (rats treated with CsA plus ENAP, n=10). Chroinc CsA nephropathy was induced by administration of CsA at a dose of 25 mg/kg/day for 4weeks and ENAP was given at a dose of 50mg/L in tap water.
During
4weeks study period, blood pressure, renal function and plasma renin activity were evaluated weekly. At the end of study, animals were sacrificed and histologic evaluation was made by vacuolization index and inclusion body index in proximal
tubules.
@ES The results were as follows :
@EN 1. The BUN and serum creatinine levels of three groups showed significant differerences according to time interval (P=0.0001). The BUN levels in ENAP group were significantly higher than control group at week 3 and 4 but lower than CsA group
at
week
4 (P<0.05, respectively). The serum creatinine levels in ENAP group were significantly higher than control group at week 2, 3 and 4 but lower than CsA group at week 2, 3 and 4 (P<0.05, respectively).
2. The creatinine clearance of three groups showed significantl differences according to time interval (P=0.0001). The creatinine clearances in ENAP group were signficantly lower than control group at week 3 and 4 but higher than CsA group at
week
3
and 4 (P<0.05, respectively).
3. The plasma renin acitivities of three groups showed significant changes during study period (P=0.0001). Plasma renin activities in ENAP group were signficantly higher than control group at week 1, 2, 3 and 4 (P<0.05, respectively) and CsA
proup
at
week 1, 2 and 3 (P<0.05, respectively).
4. There was a positive correlation between serum creatinine levels and plamsa renin acitvities (r=0.71, P<0.01).
5. Vacuolization index and inclusion index in ENAP group were significantly lower than CsA group (0.8±0.2 vs. 1.9±0.2 vs. 44.2±12.8, P<0.05, respectively).
These results suggests that activation of RAS is associated with chronic CsA nephropathy and blockage of RAS by ENAP conferred protection against the renal dysfunction and histologic lesion caused by CsA.
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KEYWORD
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