Effect of the calcium channel blocker nitrendipine in normotensive and spontaneously hypertensive, diabetic rats on kidney morphology and urinary albumin excretion.
OBJECTIVE
To investigate the effect of nitrendipine on the development of renal changes in experimental diabetes.


METHODS
Streptozotocin (STZ)-induced diabetic normotensive Wistar rats (WIS) and spontaneously hypertensive rats (SHR) were randomly allocated to nitrendipine treatment (250 mg/kg fodder) or placebo treatment for 6 months.


METHODS
Blood pressure was assessed by the tail-cuff method, urinary albumin excretion (UAE) was determined, and glomerular basement membrane (GBM) thickness, mesangial volume, and mean glomerular volume (MGV) were estimated by morphometric measurements.


RESULTS
In diabetic WIS, nitrendipine significantly reduced UAE after 2 months of treatment (P< 0.05), while no effect was was seen after 4-6 months. In diabetic SHR, no effect on UAE was seen at any time. Nitrendipine was unable to inhibit the renal and glomerular enlargement in diabetic WIS and SHR. Diabetes plus hypertension was associated with significant increase in GBM thickness, while diabetes or hypertension alone showed no significant increase in GBM. Nitrendipine treatment was unable to prevent increased GBM in diabetic SHR.


CONCLUSIONS
Nitrendipine inhibits an early increase in UAE in normotensive, diabetic rats, but fails to sustain this effect in long-term diabetes. No effect of nitrendipine was observed in SHR.
Institute of Experimental Clinical Research, Medical Research Laboratory, Aarhus University Hospital, Denmark. BirgitteNielsen@dadlnet.dk
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Nielsen
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Grønbaek
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Osterby
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Flyvbjerg
D000419:Albuminuria / Q000188:drug therapy*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000652:urine; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D009568:Nitrendipine / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013311:Streptozocin
D002121:Calcium Channel Blockers; D013311:Streptozocin; D009568:Nitrendipine