Dipyridamole prevents diabetes-induced alterations of kidney function in rats.
One possible factor for glomerular hyperfiltration in early diabetes could be a deficiency of renal vasoconstrictive mechanisms. Dipyridamole (DIP) inhibits cellular uptake of adenosine thereby increasing interstitial adenosine concentration. The effect of DIP on tubuloglomerular feedback (TGF) and on urinary protein excretion (UPE), glomerular filtration rate (GFR), and kidney weight was studied in early diabetes in rats. One day after onset of streptozotocin (STZ)-induced insulin-dependent diabetes mellitus (IDDM) daily treatment with DIP (50 mg/100 g twice a day via a gastric tube) was started in one group (STZ-DIP) and with vehicle alone in another group (STZ). Rats were housed in metabolic cages for 24 h to measure UPE 7, 14, and 21 days after STZ-injection. Non-diabetic animals, also receiving vehicle, served as controls (CON). While 7, 14, and 21 days after STZ-injection UPE was enhanced by 88, 123, and 153% in the STZ-group (n = 5) as compared to the CON-group (n = 6), the increase in UPE in the STZ-DIP-group (n = 5) was reduced by 82, 66, and 60%, respectively. Subsequently these diabetic rats were prepared for clearance and micropuncture study. Weight-matched (wm) non-diabetic rats served as controls (CONwm). TGF activity was assessed as the difference between stop flow pressures (delta SFP) in the early proximal tubule at 0 and 50 nl/min perfusion rates of Henle's loop. delta SFP was 8.8 +/- 0.7 mmHg (mean +/- SEM) in the CONwm-group (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Vallon
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V
Department of Pharmacology, University of Tübingen, Germany.
Osswald
H
H
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004176:Dipyridamole / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D004176:Dipyridamole; D000241:Adenosine