Extensive Handling of Rats Leads to Mild Urinary Bladder Hyperplasia

The urinary and urothelial effects of the frequent handling necessary for obtaining fresh-voided urine specimens were evaluated in 5-wk-old male F-344 rats fed control diet or diet containing 7.5% sodium saccharin. Frequent handling consisted of holding rats by the back of the neck in a position to obtain fresh-voided urine directly into centrifuge tubes 3 times per week for 10 weeks, whereas seldomly handled control rats received this treatment only twice during the entire 10 weeks. The urothelium of frequently handled rats fed control diet showed superficial necrosis and regenerative hyperplasia as observed by light and scanning electron microscopy. These changes were not observed in rats fed control diet that were seldomly handled. The necrosis and hyperplasia were not as pronounced in frequently handled rats fed control diet as in seldomly handled, sodium-saccharin-treated rats, but handling also potentiated the severity of the changes produced by sodium saccharin feeding. The urothelial exfoliation and consequent regenerative hyperplasia are likely secondary effects of stress.