Pioglitazone prevents corporal veno-occlusive dysfunction in a rat model of type 2 diabetes mellitus.
OBJECTIVE
To determine whether corporal veno-occlusive dysfunction (CVOD), corporal smooth muscle (SM) loss, fibrosis and oxidative stress occur in a rat model of type 2 diabetes, and whether these are counteracted by pioglitazone, as pioglitazone is vasculoprotective, and corporal SM is an extension of arterial SM.


METHODS
Male obese Zucker fa/fa rats were fed chow containing 0%, 0.001% or 0.02% pioglitazone for 2 or 5 months, using untreated lean Zucker and Fischer 344 rats as controls. Functional changes were determined by dynamic-infusion cavernosometry. Histological changes were assessed by histochemistry and immunohistochemistry followed by quantitative image analysis and/or quantitative Western blot.


RESULTS
CVOD was detected at 4.5 months of diabetes, accompanied by a lower corporal SM/collagen ratio, and increases in collagen, collagen III/I ratio, apoptotic index, and systemic and tissue oxidative stress. In the short-term treatment, high-dose pioglitazone normalized glycaemia and ameliorated fibrosis and oxidative stress, but induced CVOD, whereas the effects with the low dose were not significant. However, low-dose pioglitazone for 5 months corrected all alterations.


CONCLUSIONS
Type 2 diabetes in Zucker fa/fa rats was associated with penile corporal fibrosis, oxidative stress, and CVOD, which were ameliorated by long-term low-dose pioglitazone, suggesting that this drug might protect the SM, independently from its antidiabetic effect.
Kovanecz
Istvan
I
Department of Surgery, Urology Research Laboratory, Division of Urology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Ferrini
Monica G
MG
Vernet
Dolores
D
Nolazco
Gaby
G
Rajfer
Jacob
J
Gonzalez-Cadavid
Nestor F
NF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000473:pathology; D005355:Fibrosis; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D018783:Impotence, Vasculogenic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D010413:Penis / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker
D007004:Hypoglycemic Agents