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Urethral smooth muscle (USM) contributes to urinary continence by contracting during the urine storage phase, which is mainly mediated by activation of postjunctional α 1 -adrenoceptors. Males and females show differences in the functioning of the lower urinary tract and the most common urinary tract symptoms (LUTS). LUTS in men typically occur in association with bladder outlet obstruction, whereas in women urinary urge-incontinence symptoms are more common. Therefore, this study aimed to evaluate sex differences in α 1 -adrenoceptor subtype expression and their importance in proximal urethra contraction in the mouse (C57BL6/J) and marmoset ( Callithrix jacchus). Contractile responses to phenylephrine, norepinephrine, potassium chloride (KCl), and electrical-field stimulation (EFS) were evaluated. Phenylephrine, norepinephrine, KCl, and EFS produced markedly greater contractions in male mice and marmoset USM compared with females. The sex differences remained unchanged by N ω -nitro-l-arginine (l-NAME; nitric oxide synthase inhibitor), atropine (muscarinic receptor antagonist), and PPADS (P2X1-purinoceptor antagonist). Additionally, selective α 1A  (but not α 1B - and α 1D -)-adrenoceptor antagonists significantly reduced phenylephrine-induced USM contractions. qRT-PCR for α 1A -,  B -, and  D -adrenoceptor subtypes revealed a marked presence of the α 1A -adrenoceptor subtype in male USM, but not females. Male mouse urethra also exhibited a higher tyrosine hydroxylase mRNA expression. Histomorphometric analysis showed a greater USM area in male than female mice. In conclusion, male mouse and marmoset proximal USM shows strong α 1A - adrenoceptor-induced contractions and abundant α 1A -adrenoceptor expression, whereas α 1A -adrenoceptor-mediated mechanisms are much less important in females. The differential expression of α 1 -adrenoceptors in the proximal urethra may contribute to the higher incidence of urinary incontinence in women and obstructed voiding in men.

american journal of physiology. renal physiology./american journal of physiology. renal physiology

How important is the α<sub>1</sub>-adrenoceptor in primate and rodent proximal urethra? Sex differences in the contribution of α<sub>1</sub>-adrenoceptor to urethral contractility

How important is the α1-adrenoceptor in primate and rodent proximal urethra? Sex differences in the contribution of α1-adrenoceptor to urethral contractility

How important is the α₁-adrenoceptor in primate and rodent proximal urethra? Sex differences in the contribution of α₁-adrenoceptor to urethral contractility