Abstract
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 insulindependent 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 STZinjection. 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 (CONSwm). TGF activity was assessed as the difference between stop flow pressures (ASFP) in the early proximal tubule at 0 and 50 nl/min perfusion rates of Henle's loop. ASFP was 8.8±0.7 mmHg (mean±SEM) in the CONwm-group (n = 5). In the STZ-group (n = 5) TGF activity was reduced while in the STZ-DIP-group (n = 5) TGF activity was restored to normal values (4.7 ± 0.9 vs 11.5±1.1 mmHg). GFR was increased by 14% in the STZ-group compared to the CONwm-group, whereas in the STZ-DIP-group GFR was normal. Kidney weight measured 3 to 4 weeks after STZ was increased by 24% in the STZ-group compared to the CON-group (1.73±0.02 vs 1.40±0.03 g), whereas no significant increase in kidney weight was found in the STZ-DIP-group (1.52±0.07g). In summary, daily treatment with DIP corrected the early changes in the diabetic kidney although blood glucose levels were unaltered. We suggest that the beneficial effect on renal function in early IDDM by dipyridamole could be due to an increase of the interstitial adenosine concentration in the kidney.
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Correspondence to: H. Osswald at the above address
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Vallon, V., Osswald, H. Dipyridamole prevents diabetes-induced alterations of kidney function in rats. Naunyn-Schmiedeberg's Arch Pharmacol 349, 217–222 (1994). https://doi.org/10.1007/BF00169840
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DOI: https://doi.org/10.1007/BF00169840