The contribution of systemic hypertension to progression of chronic renal failure in the rat remnant kidney: effect of treatment with an angiotensin converting enzyme inhibitor or a calcium inhibitor

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Abstract
In order to establish if pharmacological treatment of systemic hypertension modifies the course of progressive renal failure, we studied the effects of an angiotensin converting enzyme inhibitor and a calcium antagonist, on the renal structure and function in the remnant kidney model of chronic renal failure in the rat Progressive renal failure was induced in adult female Sprague Dawley rats (SDR) by surgical removal of the right kidney, and segmental infarction of seven-eighths of the left kidney. Following subtotal nephrectomy, plasma creatinine rose from 65 ± 16 µmol/l to 173 ± 19 µmol/l (P < 0.001) over a period of 6 weeks, systolic blood pressure (SBP) rose from 121 ± 2 mmHg to 176 ± 7 mmHg (P < 0.001) and urinary protein excretion from 0.6 ± 0.2 to 84 ± 22 mg/24 h (P < 0.001). Glomerular mesangial expansion was present after 2 weeks, then progressed, in association with the development of glomerular sclerosis, which became prominent after 6 weeks Rats were treated with enalapril (5 mg/kg per day) or felodipine (30 mg/kg per day) from 1 week after subtotal nephrectomy, and their course compared with that of untreated rats. Systemic SBP decreased to a similar degree by both drug treatments. Six weeks after surgery, plasma creatinine concentration was lower in the enalapril-treated group (110 ± 8 µmol/l, P < 0.05) than in the felodipine-treated group (153 ± 23 µmol/l). The latter group showed similar plasma creatinine concentrations to those of the untreated rats (173 ± 19 µmol/l). Urinary protein excretion was reduced to 15 ± 3 mg/24 h (P < 0.001) by enalapril treatment, and increased to 221 ± 35 mg/24 h by felodipine treatment. The glomerulosclerosis index (obtained from a histological score) was reduced by enalapril but not by felodipine Despite the similar effects of enalapril and felodipine on systemic arterial blood pressure, both functional and structural damage in the rat remnant kidney model of chronic renal failure was ameliorated only by treatment with the angiotensin converting enzyme inhibitor enalapril, but not by the calcium inhibitor felodipine These results suggest that angiotensin converting enzyme inhibitors may have specific intrarenal effects that retard the deterioration of renal function that occurs when renal mass has been reduced

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