Short-term effects of quinapril and nifedipine on early renal changes in streptozotocin-induced diabetes in rats.
The effects on renal function of quinapril, an angiotensin I converting enzyme (ACE) inhibitor, and of nifedipine, a dihydropyridine calcium antagonist, were studied in the early stages of diabetes in rats. Wistar rats received one injection of streptozotocin (STZ) to induce diabetes; the hyperglycaemia was then controlled with daily insulin therapy (2-3 units NPH insulin/rat). One week after STZ injection, rats were treated orally with quinapril (0.3 or 3 mg/kg/d) or nifedipine (30 mg/kg/day) for 1 week, after which renal functions were compared with those of untreated diabetic rats or non-diabetic control rats. At the end of these two weeks, diabetic rats had gained less weight and had developed renal hypertrophy and glomerular hyperfiltration (3.21 +/- 0.23 vs 2.36 +/- 0.09 ml/min for non-diabetic rats, mean +/- SEM, P < 0.01). Their urinary albumin excretion was higher, as was the urinary excretion of water, sodium, potassium, urea and glucose. One week treatment with quinapril or nifedipine had no significant effect on the increase in the glomerular filtration rate (respectively 2.97 +/- 0.18 and 2.99 +2- 0.15 ml/min). Quinapril and nifedipine differed with regard to their effects on urinary albumin excretion. Albuminuria was increased by nifedipine but not by quinapril (respectively 0.554 +/- 0.158 and 0.149 +/- 0.046 mg/day/100 g BW, P < 0.05). This difference between the effects of the dihydropyridine and the ACE inhibitor on albuminuria may be linked to different effects on the glomerular functions.
Institut de pharmacologie, URA D0589 CNRS, Université Louis Pasteur, Strasbourg, France.
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Petitjean
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Vloemans
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Barthelmebs
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Stephan
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Grima
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Jund
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Imbs
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D000077583:Quinapril; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D002245:Carbon Dioxide; D007703:Peptidyl-Dipeptidase A; D009543:Nifedipine; D000077583:Quinapril; D010100:Oxygen