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Pioglitazone prevents corporal veno-occlusive dysfunction in a rat model of type 2 diabetes mellitus.

Kovanecz I, Ferrini MG, Vernet D, Nolazco G, Rajfer J, Gonzalez-Cadavid NF

Department of Surgery, Urology Research Laboratory, Division of Urology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

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. MATERIALS AND 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. CONCLUSION: 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.

Published 11 July 2006 in BJU Int, 98(1): 116-24.
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