Disparate effects of angiotensin converting enzyme inhibitor and calcium blocker treatment on the preservation of renal structure and function following subtotal nephrectomy or streptozotocin-induced diabetes in the rat.
Sprague-Dawley rats subjected to subtotal (1 7/8) nephrectomy or streptozotocin diabetes were treated with an angiotensin converting enzyme inhibitor or a calcium channel blocker and their course compared with untreated control animals. Subtotal nephrectomy led to hypertension, proteinuria, reduced creatinine clearance, and glomerulosclerosis over 6 weeks. Enalapril treatment (5 mg/kg/day, n = 11) or felodipine (30 mg/kg/day, n = 11) reduced systolic blood pressure to a comparable degree. Plasma creatinine (mumol/l) was lower after enalapril treatment (110 +/- 8, p less than 0.05) than with felodipine treatment (153 +/- 27) or no treatment (173 +/- 19, n = 18). Proteinuria (mg/24 h) was lower with enalapril treatment (15 +/- 3, p less than 0.001) than with no treatment (85 +/- 22) and increased with felodipine (221 +/- 35). Glomerulosclerosis was reduced with enalapril but not felodipine treatment. Diabetic rats were treated with enalapril (5 mg/kg/day, n = 17), verapamil (5 mg/kg/day, n = 17), or untreated. Diabetic rats had increased creatinine clearance (ml/min) compared with nondiabetic controls (1.52 +/- 0.06 vs. 1.15 +/- 0.05, n = 11, p less than 0.01). Enalapril and verapamil treatment reduced blood pressure equally. Enalapril but not verapamil reduced the elevated creatinine clearance of diabetic rats (enalapril, 1.37 +/- 0.04 ml/min, p less than 0.01; verapamil, 1.49 +/- 0.5 ml/min). Proteinuria (mg/24 h) was lower (p less than 0.05) with enalapril treatment (36 +/- 3) but not with verapamil treatment (58 +/- 10) in comparison to that in untreated diabetes (71 +/- 18).(ABSTRACT TRUNCATED AT 250 WORDS)
Jackson
B
B
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Cubela
R
R
Debrevi
L
L
Whitty
M
M
Johnston
C I
CI
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000209:etiology; D004656:Enalapril / Q000494:pharmacology; D015736:Felodipine; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000209:etiology; D009392:Nephrectomy; D009568:Nitrendipine / Q000031:analogs & derivatives / Q000494:pharmacology; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004656:Enalapril; D009568:Nitrendipine; D014700:Verapamil; D015736:Felodipine