Veterinary session

Feline lower urinary tract diseases (FLUTD) are commonly spread amongst domestic cats around the world, hence their clinical importance is outstanding. Lower urinary tract diseases can be caused by urolithiasis, neoplasia, bacterial urinary tract infections and anatomical abnormalities. If the underlying causes remain unknown, the disease is called feline idiopathic cystitis (FIC). The complete pathogenesis of this disease is not yet fully understood, but former studies strongly suggest that chronic stress as an environmental factor may play an important role in the pathogenesis of FIC. Since more than 50% of lower urinary tract diseases in cats are diagnosed as FIC, the further examination of its pathogenesis is very important.

To mimic the effects of chronic, recurrent stress one of the most important stress hormones involved in this disease, norepinephrine (NE) was used in an intermittent release on the cultured cells to reveal its role in the pathogenesis of FIC. In order to assess the molecular effects of this factor regardless of others a feline primary uroepithelial cell culture was established to serve as an in vitro model of the disease. Uroepithelial cells were gained from the mucosa of the bladder of a previously euthanized cat, and they were cultured for 6 days. Then the cells were exposed to 10, 100 and 1000 μmol/l norepinephrine treatment to mimic chronic intermittent stress, for 3x1 hour in addition with an hour regeneration time in between the treatments and then it was assessed that how it affected the cell’s inflammatory response, redox state and barrier function.

Our results showed that the applied norepinephrine treatment was able to trigger pro-inflammatory response and to induce oxidative stress by increasing the concentration of SDF-1 (stromal cell-derived factor) and H2O2 in cell culture media. Further examinations showed that intermittent release of norepinephrine increased cell permeability by decreasing glycosaminoglycan (GAG) concentrations, the abundance of the tight junction protein claudin-4 and the TER values confirming that norepinephrine could decrease the barrier function of the uroepithelial cells. Based on these results it can be concluded that the intermittent release of norepinephrine – such as in chronic stress – has a direct molecular effect on uroepithelial cells resulting in inflammation, increased cell membrane permeability and oxidative stress confirming that norepinephrine has a key role in the pathogenesis of chronic FIC, and that the increased norepinephrine concentrations detected in affected animals may be the cause of the changes in bladder wall.