Effect of alpha 1D-adrenoceptor blocker for the reduction of ureteral contractions

Purpose: Urolithiasis is a common urinary tract disease with growing prevalence. Alpha1-adrenoceptors (alpha 1-ARs) are abundant in ureteral smooth muscle, distributed with different alpha 1-AR subtypes. alpha 1D-AR is the most widely distributed in the ureter. However, the effect of alpha 1D-AR blockade on ureteric contraction remains unknown. Materials and Methods: We dissected smooth muscle tissues (3 mmx3 mm) from the rat bladder and human ureter, tied silk strips on both tissue ends, and measured contraction in an organ bath chamber. Contraction activity in ureteral smooth muscle cells (USMCs) was immunocytochemically examined using primary rat and human USMC cultures. Results: Using the organ bath system, we determined the inhibitory effects of silodosin, tamsulosin, and naftopidil. Naftopidil significantly decreased contractility of rat bladder tissue; similar results were observed in human ureteral tissue. To confirm ex vivo experimental results in vitro, we examined the phosphorylation of myosin light chain (MLC), a marker of contractility, in a primary human USMC culture. The examined drugs decreased phospho-MLC levels in human USMCs; however, naftopidil profoundly increased MLC dephosphorylation. Conclusions: We studied the effects of naftopidil, an alpha 1D-AR inhibitor, on the ureter. Compared with alpha-blockers, naftopidil significantly relaxed ureteral smooth muscle. Therefore, naftopidil could be an effective therapy for patients with ureteral stones.