Diabetic nephropathy in the rat: differing renal effects of an angiotensin converting enzyme inhibitor and a calcium inhibitor.
The renal functional alterations that occurred in streptozotocin-induced diabetes in uninephrectomized rats were studied over a three-month period. Diabetic animals had elevated systemic systolic blood pressure, creatinine clearance and urinary protein excretion. After three months, systolic blood pressure was 131 +/- 2 mmHg, creatinine clearance was 1.52 +/- 0.06 ml/min and urinary protein excretion 70.8 +/- 17.9 mg/24 h. Non-diabetic control rats had a systolic blood pressure of 117 +/- 3 mmHg (p less than 0.001), creatinine clearance of 1.15 +/- 0.05 ml/min (p less than 0.001), and protein excretion of 8.22 +/- 0.2 mg/24 h (p less than 0.001). Diabetic rats were treated with enalapril or verapamil, 5 mg.kg-1.day-1 which reduced systolic blood pressure to 108 +/- 3 mmHg (p less than 0.001) and 114 +/- 2 mmHg (p less than 0.001) respectively. Treatment with enalapril reduced the degree of proteinuria at three months (36.4 +/- 3.0 mg/24 h, p less than 0.05). Protein excretion rate in verapamil treated rats was 57.7 +/- 10.1 mg/24 h at three months, similar to that of untreated diabetic rats. Filtration fraction of untreated diabetic rats was 0.40 +/- 0.04. Treatment with enalapril lowered filtration fraction (0.26 +/- 0.02, p less than 0.01) whilst verapamil had no significant effect (0.37 +/- 0.02). The differing effects of enalapril and verapamil on renal function occurred despite similar degrees of hypotension, and may reflect the different intrarenal haemodynamic effects of these drugs.
Whitty
M R
MR
Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
Jackson
B
B
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D011507:Proteinuria; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014700:Verapamil / Q000494:pharmacology*
D004656:Enalapril; D014700:Verapamil