Abstract
Introduction and AimPostmenopausal women exhibit overactive bladder (OAB), as evidenced by urgency, frequency and noctúria (1). Ovariectomized (OVX) rats display OAB and urethral hypercontractility that is normalized by in vivo testosterone replacement (2). Androgen receptors (AR) have been found in urinary bladder, suggesting they play an important role in the urinary continence (3,4). However, the mechanism of action of testosterone in urethra of female rats has not been elucidated. L‐type voltage‐operated calcium channels (VOCC) are implicated in urinary contraction during the voiding phase (4). We hypothesized here that testosterone via VOCC activation regulates the female urethra. This study aimed therefore to evaluate the effects of testosterone and its modulation by VOCC on urethra contractility in OVX rats.Materials and methodsTwo‐month old female Sprague Dawley rats were submitted to bilateral ovariectomy, whereas Sham‐operated rat were manipulated but the ovaries were left intact. After 4‐month OVX, the urethra was removed, and concentration‐response curves to calcium chloride (CaCl2; 10 μM – 300 mM) were performed in the presence of testosterone (100 nM; 30 min), vehicle (alcohol; 0.5 μL) and/or the VOCC inhibitor nifedipine (3 nM; 30 min).ResultsBilateral OVX significantly increased the urethra contraction to compared with Sham group (P < 0.05). Testosterone (100 nM prevented CaCl2‐induced urethral hypercontractility in OVX group. Pre‐incubation with nifedipine (3 nM) also reduced the contractile response to extracellular calcium in OVX group. In Sham group, testosterone and/or nifedipine had no effects.ConclusionOur data suggests that testosterone via non‐classical genomic pathway acts to inhibit VOCC to normalize the urethral hypercontractility in OVX rats.All animal procedures were approved by the Ethical Committee on Animals Use CEUA/UNICAMP (CEUA; No. 4421‐1, 5250‐1).Support or Funding InformationFINANCIAL SUPPORT: FAPESP (2017/26564‐9).
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