L-dopa and streptozotocin-induced diabetic nephropathy in rats.
The purpose of the present study was to determine whether the physiological dopamine prodrug, L-dopa, could suppress streptozotocin-induced diabetic glomerular hyperfiltration, and thus prevent further evolution of the diabetic nephropathy. Male Wistar rats treated with streptozotocin (60 mg/kg, intravenously) rapidly developed hyperglycemia which was stabilized (congruent to 4 g/L) by a daily insulin injection. Within two weeks, a significant increase in glomerular filtration rate (GFR) and a rise in the filtration fraction were observed as described in the early stage of diabetic nephropathy. Increase in both GFR and in the filtration fraction were normalized by treating the rats with L-dopa (10 mg/kg, subcutaneously, twice a day for one week). The effects of L-dopa were linked to endorenal DA synthesis and to DA-1 receptor stimulation since both carbidopa and SCH 23390 suppressed them.
Barthelmebs
M
M
Institut de Pharmacologie, URA D0589 CNRS, Université Louis Pasteur, France.
Vailly
B
B
Velly
J
J
Grima
M
M
Imbs
J L
JL
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D018492:Dopamine Antagonists; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D001552:Benzazepines; D018492:Dopamine Antagonists; D007980:Levodopa; D013311:Streptozocin; D002230:Carbidopa