Evidence for predominant mediation of alpha(1)-adrenoceptor in the tonus of entire urethra of women

Purpose: We separated the entire length of the isolated human female urethr a into seven parts from external urethral meatus to bladder neck and examin ed regional differences in contractile responses to noradrenaline, clonidin e, acetylcholine and KCI. Materials and Methods: The entire urethra was obtained from 9 female patien ts with a mean age of 72.2 +/- 1.8 years. The entire urethra (35 to 42 mm. in length) was transversely cut into seven parts, and the contractile respo nses to noradrenaline, clonidine, acetylcholine and KCl of these parts were examined. Results: Noradrenaline but not clonidine produced concentration-dependent c ontraction in all parts, with a peak amplitude in middle to proximal urethr a. In contrast, acetylcholine produced contraction only in proximal urethra and bladder neck. The amplitudes of noradrenaline-induced contraction were normalized against those induced by KCl, revealing similarity in patterns between noradrenaline-induced contractions and urethral pressure profile in human female urethra. These contractions to noradrenaline and acetylcholin e were competitively inhibited by prazosin (pK(B): 8.38 +/- 0.10) and atrop ine (pK(B): 8.52 +/- 0.43), respectively. Conclusion: These findings suggest that sympathetic innervation helps maint ain resting urethral tonus, mainly through alpha(1)-adrenoceptors.