The remnant kidney model of chronic renal failure was established in female Sprague-Dawley rats subjected to surgical removal of the right kidney and segmental infarction of seven-eighths of the left kidney. Plasma creatinine (mumol/l) rose from 65 (s.e.m. = 16, n = 18) to 153 (s.e.m. = 27, t-test, P less than 0.001, d.f. = 17) over 6 weeks. Histological glomerulosclerotic lesions were present from 2 weeks and prominent by 6 weeks post-surgery. Rats were treated with enalapril (5 mg/kg per day, n = 11) or felodipine (30 mg/kg per day, n = 13) from 1 week post-surgery, and their course compared to untreated rats (n = 18). Blood pressure (mmHg) was lowered by both treatments. Six weeks post-nephrectomy, systolic blood pressure in the untreated group was 176 (s.e.m. = 7, n = 18), enalapril group 122 (s.e.m. = 5, t-test, P less than 0.001, d.f. = 27), and felodipine group 128 (s.e.m. = 3, t-test, P less than 0.001, d.f. = 29). Plasma creatinine (mumol/l) was lower in the enalapril group (110, s.e.m. = 8, t-test, P less than 0.05, d.f. = 27) but not the felodipine group (173, s.e.m. = 19, t-test, n.s.) 6 weeks after subtotal nephrectomy compared to the untreated group (153, s.e.m. = 27). Glomerulosclerosis (blinded histological score) was reduced with enalapril treatment (1.93, s.e.m. = 0.03, t-test, P less than 0.05, d.f. = 27) but not felodipine treatment (2.15, s.e.m. = 0.04, c.f. untreated 2.36, s.e.m. = 0.12, t-test, n.s.). Urinary protein excretion (mg/24 h) was 84 (s.e.m. = 22, n = 13) in untreated rats, 15 (s.e.m. = 3, t-test, P less than 0.001, d.f. = 22) in enalapril-treated rats and 221 (s.e.m. = 35, n = 10) with felodipine treatment. Functional and structural damage in the rat remnant kidney model of chronic renal failure was ameliorated by treatment with enalapril but not by treatment with felodipine.

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To ascertain the contribution of systemic hypertension in the progression of renal failure, we have studied the effects of pharmacological treatment of hypertension in rats with the remnant kidney model of renal insufficiency, streptozotocin diabetes, or nephrotoxic serum nephritis.Treatment with the angiotensin converting enzyme (ACE) inhibitor enalapril lowered systemic blood pressure in the remnant kidney and diabetic animals, but did not lower blood pressure in rats with nephrotoxic serum nephritis.Proteinuria was reduced in all three models, and creatinine clearance improved in the remnant kidney and diabetic animals, when compared with untreated controls.In the remnant kidney and diabetic models systemic blood pressure was lowered to a similar degree by treatments with a calcium blocker, with no improvement in either proteinuria, or glomerular filtration rate. Further studies of the long-term effects of enalapril have been undertaken in rats with the two kidney one clip model of hypertension. Rats treated with enalapril had a lower blood pressure and improved survival over one year of treatment, compared with untreated rats. After 1 year of treatment however the clipped kidney was small and fibrotic, and non functional.Following withdrawal of enalapril therapy there was no functional improvement of the clipped kidney.The possibility that ACE inhibitors have a specific intra-renal effect reducing the rate of progression of renal disease now needs confirmation in human studies. In renovascular hypertension however, intra-renal changes induced by ACE inhibitors may cause irreversible renal damage. chronic renal failure ; diabetic nephropathy ; hypertension ; nephrotoxic serum nephritis ; renovascular hypertensionThe contribution of systemic hypertension to the progression of renal failure is controversial.Systemic hypertension is common in chronic renal failure, and may contribute to the progression of glomerular injury (Del Greco et al. 1975). It is well known that malignant hypertension leads to progressive renal failure, where fibrinoid necrosis of the arterioles is associated with progressive loss of renal function, and eventual endstage renal failure. The treatment of severe accelerated hypertension is associated with improvement in renal function, however the effect of antihypertensive therapy on renal functional impairment associated with milder forms of systemic hypertension is still not clear. Studies of blood pressure treatment have yielded conflicting results. In some risk factor surveys, systemic