[Prevention by L-dopa of early renal consequences of diabetes induced by streptozocin in rats].
The early renal effects associated with streptozotocin-induced diabetes in rats (glomerular hyperfiltration and increase in filtration fraction) are similar to modifications reported in the early stage of human diabetic nephropathy. We examined the reversibility of these early renal diabetic effects by dopamine, which might correct glomerular hyperfiltration thanks to its preferential vasodilatory action on glomerular efferent arterioles. A dopamine prodrug, L-dopa was used to increase endorenal dopamine synthesis. Studies were carried out on streptozotocin-treated (60 mg/kg, i.v.) Wistar rats, supplemented with NPH insulin (2 to 3 U/day) such as to stabilize hyperglycemia at 22 mmol/l. One week after diabetes induction, animals were treated during a week either with L-dopa (10 mg/kg, s.c. twice daily) or L-dopa plus a dopa-decarboxylase inhibitor, carbidopa (10 mg/kg, s.c. 30 min before each L-dopa injection) or L-dopa plus a selective D1 receptor antagonist, SCH 23390 (100 micrograms/kg, s.c., with each L-dopa injection). Control diabetic animals received the solvent of L-dopa and control non-diabetic animals received the solvent of streptozotocin. After one week of L-dopa or other treatment, the renal functions of the rats were investigated (polyfructosan and PAH clearances) under inactin anaesthesia. As expected, streptozotocin induced glomerular hyperfiltration (1.3 +/- 0.07, n = 14, versus 0.93 +/- 0.05 ml/min.g kidney weight in non-diabetic controls, p less than 0.001) and an increase in filtration fraction (52.4 +/- 5.1 versus 32.1 +/- 1.7%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Vailly
B
B
Institut de pharmacologie (URA DO 589 CNRS), université Louis-Pasteur, CHRU, Strasbourg.
Barthelmebs
M
M
Velly
J
J
Grima
M
M
Imbs
J L
JL
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D005919:Glomerular Filtration Rate; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D013311:Streptozocin
D001786:Blood Glucose; D007980:Levodopa; D013311:Streptozocin
Prévention par la L-dopa des conséquences rénales précoces du diabète à la streptozocine chez le rat.