Effect of L-dopa decarboxylase inhibitor benserazide on renal function in streptozotocin-diabetic rats.
OBJECTIVE
Benserazide (BZD), an inhibitor of the dopamine synthesis, abolished the increase in glomerular filtration rate (GFR) following the infusion of a mixed amino acid solution. These results reveal endogenous dopamine as a mediator in the renal response to amino acids. The aim of the present study was to evaluate whether dopamine is also involved in the regulation of glomerular hyperfiltration during the early state of diabetes mellitus (DM).


METHODS
Male Sprague-Dawley rats were injected with a single dose of streptozotocin (60 mg/kg i.p.) for induction of experimental DM (n = 7-8/group). Age-matched non-diabetic animals, injected with citrate buffer, served as controls (CON, n = 8/group). Clearance experiments were performed 2 weeks after induction of DM in thiopental-anesthetized rats (80 mg/kg i.p.), which were continuously infused either with BZD (30 microg/min/kg) or vehicle (VHC).


RESULTS
Mean arterial blood pressure was around 110 mm Hg and did not significantly differ among the groups. GFR was 0.95 +/- 0.02 ml/min/100 g b.w. in VHC-treated CON. BZD treatment did not significantly change GFR in the CON group (0.92 +/- 0.06 ml/min/100 g b.w.). As expected, glomerular hyperfiltration was observed in diabetic rats infused with VHC (1.24 +/- 0.08 ml/min/100 g b.w.). Treatment with BZD significantly reduced the diabetes-induced increase in GFR to control levels (0.95 +/- 0.05 ml/min/100 g b.w.).


CONCLUSIONS
Our results show that the inhibition of dopamine synthesis prevented the increase in GFR due to diabetic conditions, indicating that endogenous dopamine is involved in the regulation of DM-induced changes in renal hemodynamics.
Pfeil
Katrin
K
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tübingen, Tübingen, Germany.
Staudacher
Torsten
T
Luippold
Gerd
G
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology*; D004296:Dopa Decarboxylase / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014556:Urine
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D015259:Dopamine Agents; D001545:Benserazide; D004296:Dopa Decarboxylase; D004298:Dopamine