The effect of vardenafil (a PDE type 5 inhibitor) on renal function in the diabetic rabbit: a pilot study.
BACKGROUND
Diabetic nephropathy is a common cause of impaired renal function. We investigated the effect vardenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, has on renal function in the diabetic rabbit.


METHODS
Blood was taken at 4 and 6 months from control and alloxan-induced diabetic animals (n=8, in each group) and biochemical variables pertaining to renal function determined. A 7-month sample was also analysed after giving control and diabetic animals (n=4 in each group) either vardenafil (3 mg/kg) or vehicle to drink for 4 weeks. Spot urine total protein/ creatinine ratio (TP/C) was determined at 4 and 6 months. At 7 months a 24 h-urine sample was collected to measure TP/C and creatinine clearance (CrCl).


RESULTS
There was a significant increase in serum creatinine concentration after 6 months diabetes, which was significantly reduced by vardenafil. TP/C from diabetic rabbit spot urine samples at 6 months were significantly elevated compared to control animals, indicating the presence of proteinuria. Vardenafil treatment caused a normalisation of TP/C. Diabetic animals receiving vardenafil showed a significant improvement in CrCl when compared with diabetic animals given vehicle.


CONCLUSIONS
These findings highlight a potential role for vardenafil in the treatment of diabetic nephropathy.
Lau
David H
DH
Department of Clinical Biochemistry, Royal Free Hospital and University College Medical School, University College London, Hampstead Campus, Rowland Hill Street, London NW3 2PF, UK.
Mikhailidis
Dimitri P
DP
Thompson
Cecil S
CS
D000284:Administration, Oral; D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D003401:Creatine / Q000097:blood; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D058986:Phosphodiesterase 5 Inhibitors; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use; D000069058:Vardenafil Dihydrochloride
D004791:Enzyme Inhibitors; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000496:Alloxan; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D003401:Creatine