Upregulated Expression of TRPV1 and TRPV4 in the Urethra Following Cyclophosphamide-Induced Cystitis in Rats: A Potential Mechanism of Bladder-Urethral Dysfunction

Purpose: This study aimed to investigate the impact of cyclophosphamide (CYP)-induced cystitis on the expression of transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) in the rat urethra, and to evaluate their potential roles in urethral contribution to bladder dysfunction during inflammation.Methods: Female rats were divided into the control and CYP-treated groups to induce cystitis. After 72 hours, cystometric analysis was performed to evaluate voiding changes, and urethral TRPV1 and TRPV4 expression was assessed by Western blot and immunofluorescence.Results: Cystitis rats exhibited a significantly shorter contraction interval (5.9±1.2 minutes vs. 14.7±0.8 minutes, P<0.05) and higher contraction pressure (16.3±0.9 mmHg vs. 10.1±1.3 mmHg, P<0.05) compared to controls. TRPV1 expression was predominant in the urethral mucosal cytoplasm and smooth muscle cells, whereas TRPV4 was largely localized to the cell membranes and perimuscular connective tissues. Both TRPV1 and TRPV4 protein levels were significantly upregulated in the cystitis group (P<0.05).Conclusions: The upregulation and differential localization of TRPV1 and TRPV4 in the urethra during cystitis suggest their involvement in the pathophysiological mechanisms underlying inflammation-induced lower urinary tract dysfunction. These channels may mediate altered sensory or contractile signaling in the urethra in response to bladder inflammation.