Mechanisms involved in testosterone-induced relaxation to the pig urinary bladder neck

Abstract

Objectives: Testosterone replacement therapy improves bladder capacity in urinary tract dysfunction. There is no information, however, about the role of this steroid hormone on the muscle tension of the bladder outflow region. The current study investigated the mechanisms underlying the testosterone-induced action in the pig bladder neck.

Methods: Urothelium-denuded bladder neck strips were mounted in myographs for isometric force recordings and for simultaneous measurements of intracellular Ca(2+) concentration ([Ca(2+)](i)) and tension. The relaxations to testosterone, the non-aromatizable metabolite 4,5α-dihydrotestosterone (DHT) and electrical field stimulation (EFS) were carried out on phenylephrine (PhE)-precontracted strips.

Results: Testosterone and DHT evoked similar concentration-dependent relaxations only at very high pharmacological concentrations. The presence of the urothelium and the inhibition of intracellular androgenic receptor (AR), aromatase, 5α-reductase, nitric oxide (NO) synthase, guanylyl cyclase, cyclooxygenase (COX), large-, intermediate- and small-Ca(2+)-activated K(+) channels or ATP-dependent K(+) channels failed to modify the testosterone relaxations. Neuronal voltage-gated Ca(2+) (VOC) channels and voltage-gated K(+) (K(V)) channel blockers potentiated these responses. EFS evoked frequency-dependent relaxations, which were not changed by threshold concentrations of testosterone. In Ca(2+)-free potassium rich physiological saline solution, testosterone inhibited the contractions induced by CaCl(2) and the L-type VOC channel activator (±)-BAY K 8644. Relaxations elicited by testosterone were accompanied by simultaneous decreases in smooth muscle [Ca(2+)](i).

Conclusions: Testosterone produces relaxation of the pig urinary bladder neck through mechanisms independent of urothelium, AR, aromatase, 5α-reductase, NO synthase, guanylyl cyclase, COX and K(+) channels. Testosterone-induced relaxation is produced via the inhibition of the extracellular Ca(2+) entry through L-type VOC channels.