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Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy
J W Scholey1, P L Miller, H G Rennke
1Department of Medicine, Palo Alto Veterans Administration Medical Center, California.
Abstract:
The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Enalapril lowered blood pressure in rats with adriamycin nephrosis but did not prevent kidney function decline or glomerular sclerosis. This suggests enalapril may slow, but not halt, progressive renal injury.
Area of Science:
- Nephrology
- Pharmacology
- Experimental Medicine
Background:
- Adriamycin-induced nephrosis is a model for progressive renal injury.
- Converting enzyme inhibitors (CEIs) like enalapril are used to manage hypertension and kidney disease.
Purpose of the Study:
- To evaluate the short-term and long-term effects of enalapril on adriamycin nephrosis in rats.
- To determine if enalapril can prevent or slow the progression of renal injury and decline in glomerular filtration rate (GFR).
Main Methods:
- Munich-Wistar rats received adriamycin, followed by enalapril treatment in experimental groups.
- Micropuncture studies assessed hemodynamic parameters and albuminuria.
- Glomerular filtration rate (GFR) and glomerular sclerosis were evaluated over four and six months.
Main Results:
- Short-term enalapril reduced blood pressure and glomerular capillary pressure but did not affect albuminuria or GFR.
- Chronic enalapril treatment lowered blood pressure without reducing albuminuria.
- Enalapril blunted the reduction in GFR over time but did not prevent it.
- Glomerular sclerosis developed in both treated and untreated rats.
Conclusions:
- Enalapril effectively reduces blood pressure in adriamycin nephrotic rats.
- While enalapril may slow the decline in GFR, it does not halt the progression of renal injury or prevent glomerular sclerosis in this model.