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

J Cardiovasc Pharmacol. 1987:10 Suppl 10:S167-9.

Abstract

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)

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Calcium Channel Blockers / therapeutic use*
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Nephropathies / drug therapy
  • Diabetic Nephropathies / etiology
  • Enalapril / pharmacology
  • Felodipine
  • Hypertension / drug therapy
  • Hypertension / etiology
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / etiology
  • Nephrectomy*
  • Nitrendipine / analogs & derivatives
  • Nitrendipine / pharmacology
  • Proteinuria / etiology
  • Rats
  • Rats, Inbred Strains
  • Verapamil / pharmacology

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Calcium Channel Blockers
  • Enalapril
  • Nitrendipine
  • Verapamil
  • Felodipine