Preservation of renal function in the rat remnant kidney model of chronic renal failure by blood pressure reduction.
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.
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006977:Hypertension, Renal / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D003404:Creatinine