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

• Published in: BJU international 2006-07, Vol.98 (1), p.116-124
• Main Authors: KOVANECZ, ISTVAN, FERRINI, MONICA G., VERNET, DOLORES, NOLAZCO, GABY, RAJFER, JACOB, GONZALEZ‐CADAVID, NESTOR F.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Associated diseases and complications; Biological and medical sciences; Blotting, Western; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - pathology; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - drug therapy; Diabetic Angiopathies - pathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; erectile dysfunction; Fibrosis; Hypoglycemic Agents - therapeutic use; Impotence, Vasculogenic - drug therapy; Impotence, Vasculogenic - pathology; Male; Medical sciences; Nephrology. Urinary tract diseases; Oxidative Stress; Penis - pathology; Rats; Rats, Zucker; smooth muscle; thiazolidenediones; Zucker fa/fa rat
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2006.06268.x

OBJECTIVES 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.