Ramipril prevents microtubular changes in proximal tubules from streptozotocin diabetic rats.
This study has investigated the microtubular cytoskeleton in rat glomerular and proximal tubule cells in experimental diabetes. The effect of treatment with ramipril on the relationship between microtubule organization and albuminuria in diabetes has also been examined. Diabetes was induced in male Sprague-Dawley rats by administration of streptozotocin (50 mg/kg, i.v.). Rats were treated with or without ramipril in their drinking water for 12 weeks. Diabetes was characterized by an increase in blood glucose level, glomerular filtration rate, and albumin excretion rate. Treatment of diabetic rats with ramipril did not affect glycaemic control, but reduced systolic blood pressure and prevented the rise in albuminuria and glomerular filtration rate. Immunohistochemistry was performed by using the ARK Peroxidase method with alpha-tubulin antibody. The regular, grainy staining pattern of the microtubules present in the renal proximal tubules from control kidneys was altered in diabetic animals, and appeared fragmented and striated. This was prevented by treatment with ramipril. Quantitative morphometric analysis revealed an increase in the percent proportional staining for alpha-tubulin in the proximal tubules of untreated diabetic rats (33.3 +/- 3.3%, n = 8, P < 0.05 vs control) compared with control rats (11.7 +/- 1.7%, n = 6), which was reduced by ramipril treatment (26.7 +/- 2.1%, n = 6, P < 0.05 vs untreated diabetic). Staining for alpha-tubulin in glomerular cells was unchanged in all groups. There was no significant difference in renal alpha-tubulin expression among all groups, as determined by real-time reverse transcription-polymerase chain reaction. These results raise the possibility that diabetes-induced changes in microtubules in the renal proximal tubules may contribute, in part, to the increase in albuminuria observed in diabetes.
Osicka
Tanya M
TM
Endocrine Unit, Department of Medicine, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia. Tanya.Osicka@med.monash.edu.au
Forbes
Josephine M
JM
Thallas
Vicki
V
Brammar
Gail C
GC
Jerums
George
G
Comper
Wayne D
WD
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000648:ultrastructure*; D008297:Male; D008870:Microtubules; D017257:Ramipril / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D017257:Ramipril