Urothelium-denuded bladder neck strips were mounted in myographs for isometric force recordings and for simultaneous measurements of intracellular Ca2+ concentration ([Ca2+]i) and tension. The relaxations to testosterone, the non-aromatizable metabolite 4,5伪-dihydrotestosterone (DHT) and electrical field stimulation (EFS) were carried out on phenylephrine (PhE)-precontracted strips.
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, 5伪-reductase, nitric oxide (NO) synthase, guanylyl cyclase, cyclooxygenase (COX), large-, intermediate- and small-Ca2+-activated K+ channels or ATP-dependent K+ channels failed to modify the testosterone relaxations. Neuronal voltage-gated Ca2+ (VOC) channels and voltage-gated K+ (KV) channel blockers potentiated these responses. EFS evoked frequency-dependent relaxations, which were not changed by threshold concentrations of testosterone. In Ca2+-free potassium rich physiological saline solution, testosterone inhibited the contractions induced by CaCl2 and the L-type VOC channel activator (卤)-BAY K 8644. Relaxations elicited by testosterone were accompanied by simultaneous decreases in smooth muscle [Ca2+]i.
Testosterone produces relaxation of the pig urinary bladder neck through mechanisms independent of urothelium, AR, aromatase, 5伪-reductase, NO synthase, guanylyl cyclase, COX and K+ channels. Testosterone-induced relaxation is produced via the inhibition of the extracellular Ca2+ entry through L-type VOC channels.